PubMed:26747427 JSON TXT

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Glycan-Motif

{"project":"Glycan-Motif","denotations":[{"id":"T1","span":{"begin":69,"end":76},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"},{"id":"T2","span":{"begin":384,"end":390},"obj":"https://glytoucan.org/Structures/Glycans/G82576YO"},{"id":"T3","span":{"begin":448,"end":455},"obj":"https://glytoucan.org/Structures/Glycans/G00021MO"},{"id":"T4","span":{"begin":448,"end":455},"obj":"https://glytoucan.org/Structures/Glycans/G54161DR"},{"id":"T5","span":{"begin":665,"end":672},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"},{"id":"T6","span":{"begin":832,"end":839},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"},{"id":"T7","span":{"begin":963,"end":970},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"},{"id":"T8","span":{"begin":990,"end":997},"obj":"https://glytoucan.org/Structures/Glycans/G00021MO"},{"id":"T9","span":{"begin":990,"end":997},"obj":"https://glytoucan.org/Structures/Glycans/G54161DR"},{"id":"T10","span":{"begin":1063,"end":1070},"obj":"https://glytoucan.org/Structures/Glycans/G00021MO"},{"id":"T11","span":{"begin":1063,"end":1070},"obj":"https://glytoucan.org/Structures/Glycans/G54161DR"},{"id":"T12","span":{"begin":1095,"end":1102},"obj":"https://glytoucan.org/Structures/Glycans/G00021MO"},{"id":"T13","span":{"begin":1095,"end":1102},"obj":"https://glytoucan.org/Structures/Glycans/G54161DR"},{"id":"T14","span":{"begin":1215,"end":1222},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"},{"id":"T15","span":{"begin":1268,"end":1275},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"},{"id":"T16","span":{"begin":1439,"end":1446},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"},{"id":"T17","span":{"begin":1645,"end":1651},"obj":"https://glytoucan.org/Structures/Glycans/G82576YO"},{"id":"T18","span":{"begin":1693,"end":1700},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"},{"id":"T19","span":{"begin":1775,"end":1782},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"}],"text":"Comparison of biological activities of human antithrombins with high-mannose or complex- type nonfucosylated N-linked oligosaccharides.\nThe structure of the N-linked oligosaccharides attached to antithrombin (AT) has been shown to affect its anticoagulant activity and pharmacokinetics. Human AT has biantennary complex-type oligosaccharides with the unique feature of lacking a core fucose, which affects its biological activities by changing its heparin binding affinity. In human plasma, AT circulates as a mixture of the α-form bearing four oligosaccharides and the β-form lacking an oligosaccharide at Asn135. However, it remains unclear how the immature high-mannose-type oligosaccharides produced by mammalian cells affect biological activities of AT. Here, we succeeded in directly comparing the activities between the high-mannose and complex-types. Interestingly, although there were no substantial differences in thrombin inhibitory activity, the high-mannose-type showed higher heparin binding affinity. The anticoagulant activities were increased by heparin and correlated with the heparin binding affinity, resulting in the strongest anticoagulant activity being displayed in the β-form with the high-mannose-type. In pharmacokinetic profiling, the high-mannose-type showed a much shorter plasma half-life than the complex-type. The β-form was found to have a prolonged plasma half-life compared with the α-form for the high-mannose-type; conversely, the α-form showed a longer half-life than the β-form for the complex-type. The present study highlights that AT physiological activities are strictly controlled not only by a core fucose at the reducing end but also by the high-mannose-type structures at the nonreducing end. The β-form with the immature high-mannose-type appears to function as a more potent anticoagulant than the AT typically found in human plasma, once it emerges in the blood."}

GlyCosmos6-Glycan-Motif-Image

GlyCosmos6-Glycan-Motif-Structure

{"project":"GlyCosmos6-Glycan-Motif-Structure","denotations":[{"id":"T1","span":{"begin":69,"end":76},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"},{"id":"T2","span":{"begin":384,"end":390},"obj":"https://glytoucan.org/Structures/Glycans/G82576YO"},{"id":"T3","span":{"begin":448,"end":455},"obj":"https://glytoucan.org/Structures/Glycans/G00021MO"},{"id":"T4","span":{"begin":448,"end":455},"obj":"https://glytoucan.org/Structures/Glycans/G54161DR"},{"id":"T5","span":{"begin":665,"end":672},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"},{"id":"T6","span":{"begin":832,"end":839},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"},{"id":"T7","span":{"begin":963,"end":970},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"},{"id":"T8","span":{"begin":990,"end":997},"obj":"https://glytoucan.org/Structures/Glycans/G00021MO"},{"id":"T9","span":{"begin":990,"end":997},"obj":"https://glytoucan.org/Structures/Glycans/G54161DR"},{"id":"T10","span":{"begin":1063,"end":1070},"obj":"https://glytoucan.org/Structures/Glycans/G00021MO"},{"id":"T11","span":{"begin":1063,"end":1070},"obj":"https://glytoucan.org/Structures/Glycans/G54161DR"},{"id":"T12","span":{"begin":1095,"end":1102},"obj":"https://glytoucan.org/Structures/Glycans/G00021MO"},{"id":"T13","span":{"begin":1095,"end":1102},"obj":"https://glytoucan.org/Structures/Glycans/G54161DR"},{"id":"T14","span":{"begin":1215,"end":1222},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"},{"id":"T15","span":{"begin":1268,"end":1275},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"},{"id":"T16","span":{"begin":1439,"end":1446},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"},{"id":"T17","span":{"begin":1645,"end":1651},"obj":"https://glytoucan.org/Structures/Glycans/G82576YO"},{"id":"T18","span":{"begin":1693,"end":1700},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"},{"id":"T19","span":{"begin":1775,"end":1782},"obj":"https://glytoucan.org/Structures/Glycans/G70323CJ"}],"text":"Comparison of biological activities of human antithrombins with high-mannose or complex- type nonfucosylated N-linked oligosaccharides.\nThe structure of the N-linked oligosaccharides attached to antithrombin (AT) has been shown to affect its anticoagulant activity and pharmacokinetics. Human AT has biantennary complex-type oligosaccharides with the unique feature of lacking a core fucose, which affects its biological activities by changing its heparin binding affinity. In human plasma, AT circulates as a mixture of the α-form bearing four oligosaccharides and the β-form lacking an oligosaccharide at Asn135. However, it remains unclear how the immature high-mannose-type oligosaccharides produced by mammalian cells affect biological activities of AT. Here, we succeeded in directly comparing the activities between the high-mannose and complex-types. Interestingly, although there were no substantial differences in thrombin inhibitory activity, the high-mannose-type showed higher heparin binding affinity. The anticoagulant activities were increased by heparin and correlated with the heparin binding affinity, resulting in the strongest anticoagulant activity being displayed in the β-form with the high-mannose-type. In pharmacokinetic profiling, the high-mannose-type showed a much shorter plasma half-life than the complex-type. The β-form was found to have a prolonged plasma half-life compared with the α-form for the high-mannose-type; conversely, the α-form showed a longer half-life than the β-form for the complex-type. The present study highlights that AT physiological activities are strictly controlled not only by a core fucose at the reducing end but also by the high-mannose-type structures at the nonreducing end. The β-form with the immature high-mannose-type appears to function as a more potent anticoagulant than the AT typically found in human plasma, once it emerges in the blood."}

sentences

Glycosmos6-MAT

{"project":"Glycosmos6-MAT","denotations":[{"id":"T1","span":{"begin":1907,"end":1912},"obj":"http://purl.obolibrary.org/obo/MAT_0000083"},{"id":"T2","span":{"begin":1907,"end":1912},"obj":"http://purl.obolibrary.org/obo/MAT_0000315"}],"text":"Comparison of biological activities of human antithrombins with high-mannose or complex- type nonfucosylated N-linked oligosaccharides.\nThe structure of the N-linked oligosaccharides attached to antithrombin (AT) has been shown to affect its anticoagulant activity and pharmacokinetics. Human AT has biantennary complex-type oligosaccharides with the unique feature of lacking a core fucose, which affects its biological activities by changing its heparin binding affinity. In human plasma, AT circulates as a mixture of the α-form bearing four oligosaccharides and the β-form lacking an oligosaccharide at Asn135. However, it remains unclear how the immature high-mannose-type oligosaccharides produced by mammalian cells affect biological activities of AT. Here, we succeeded in directly comparing the activities between the high-mannose and complex-types. Interestingly, although there were no substantial differences in thrombin inhibitory activity, the high-mannose-type showed higher heparin binding affinity. The anticoagulant activities were increased by heparin and correlated with the heparin binding affinity, resulting in the strongest anticoagulant activity being displayed in the β-form with the high-mannose-type. In pharmacokinetic profiling, the high-mannose-type showed a much shorter plasma half-life than the complex-type. The β-form was found to have a prolonged plasma half-life compared with the α-form for the high-mannose-type; conversely, the α-form showed a longer half-life than the β-form for the complex-type. The present study highlights that AT physiological activities are strictly controlled not only by a core fucose at the reducing end but also by the high-mannose-type structures at the nonreducing end. The β-form with the immature high-mannose-type appears to function as a more potent anticoagulant than the AT typically found in human plasma, once it emerges in the blood."}

GlycoBiology-FMA

uniprot-mouse

{"project":"uniprot-mouse","denotations":[{"id":"T1","span":{"begin":209,"end":211},"obj":"http://www.uniprot.org/uniprot/Q8VHK8"},{"id":"T2","span":{"begin":293,"end":295},"obj":"http://www.uniprot.org/uniprot/Q8VHK8"},{"id":"T3","span":{"begin":491,"end":493},"obj":"http://www.uniprot.org/uniprot/Q8VHK8"},{"id":"T4","span":{"begin":755,"end":757},"obj":"http://www.uniprot.org/uniprot/Q8VHK8"},{"id":"T5","span":{"begin":1574,"end":1576},"obj":"http://www.uniprot.org/uniprot/Q8VHK8"},{"id":"T6","span":{"begin":1848,"end":1850},"obj":"http://www.uniprot.org/uniprot/Q8VHK8"}],"text":"Comparison of biological activities of human antithrombins with high-mannose or complex- type nonfucosylated N-linked oligosaccharides.\nThe structure of the N-linked oligosaccharides attached to antithrombin (AT) has been shown to affect its anticoagulant activity and pharmacokinetics. Human AT has biantennary complex-type oligosaccharides with the unique feature of lacking a core fucose, which affects its biological activities by changing its heparin binding affinity. In human plasma, AT circulates as a mixture of the α-form bearing four oligosaccharides and the β-form lacking an oligosaccharide at Asn135. However, it remains unclear how the immature high-mannose-type oligosaccharides produced by mammalian cells affect biological activities of AT. Here, we succeeded in directly comparing the activities between the high-mannose and complex-types. Interestingly, although there were no substantial differences in thrombin inhibitory activity, the high-mannose-type showed higher heparin binding affinity. The anticoagulant activities were increased by heparin and correlated with the heparin binding affinity, resulting in the strongest anticoagulant activity being displayed in the β-form with the high-mannose-type. In pharmacokinetic profiling, the high-mannose-type showed a much shorter plasma half-life than the complex-type. The β-form was found to have a prolonged plasma half-life compared with the α-form for the high-mannose-type; conversely, the α-form showed a longer half-life than the β-form for the complex-type. The present study highlights that AT physiological activities are strictly controlled not only by a core fucose at the reducing end but also by the high-mannose-type structures at the nonreducing end. The β-form with the immature high-mannose-type appears to function as a more potent anticoagulant than the AT typically found in human plasma, once it emerges in the blood."}

GlycoBiology-NCBITAXON

{"project":"GlycoBiology-NCBITAXON","denotations":[{"id":"T1","span":{"begin":717,"end":722},"obj":"http://purl.bioontology.org/ontology/STY/T025"}],"text":"Comparison of biological activities of human antithrombins with high-mannose or complex- type nonfucosylated N-linked oligosaccharides.\nThe structure of the N-linked oligosaccharides attached to antithrombin (AT) has been shown to affect its anticoagulant activity and pharmacokinetics. Human AT has biantennary complex-type oligosaccharides with the unique feature of lacking a core fucose, which affects its biological activities by changing its heparin binding affinity. In human plasma, AT circulates as a mixture of the α-form bearing four oligosaccharides and the β-form lacking an oligosaccharide at Asn135. However, it remains unclear how the immature high-mannose-type oligosaccharides produced by mammalian cells affect biological activities of AT. Here, we succeeded in directly comparing the activities between the high-mannose and complex-types. Interestingly, although there were no substantial differences in thrombin inhibitory activity, the high-mannose-type showed higher heparin binding affinity. The anticoagulant activities were increased by heparin and correlated with the heparin binding affinity, resulting in the strongest anticoagulant activity being displayed in the β-form with the high-mannose-type. In pharmacokinetic profiling, the high-mannose-type showed a much shorter plasma half-life than the complex-type. The β-form was found to have a prolonged plasma half-life compared with the α-form for the high-mannose-type; conversely, the α-form showed a longer half-life than the β-form for the complex-type. The present study highlights that AT physiological activities are strictly controlled not only by a core fucose at the reducing end but also by the high-mannose-type structures at the nonreducing end. The β-form with the immature high-mannose-type appears to function as a more potent anticoagulant than the AT typically found in human plasma, once it emerges in the blood."}

GO-BP

{"project":"GO-BP","denotations":[{"id":"T1","span":{"begin":242,"end":264},"obj":"http://purl.obolibrary.org/obo/GO_0050819"},{"id":"T2","span":{"begin":1020,"end":1044},"obj":"http://purl.obolibrary.org/obo/GO_0050819"}],"text":"Comparison of biological activities of human antithrombins with high-mannose or complex- type nonfucosylated N-linked oligosaccharides.\nThe structure of the N-linked oligosaccharides attached to antithrombin (AT) has been shown to affect its anticoagulant activity and pharmacokinetics. Human AT has biantennary complex-type oligosaccharides with the unique feature of lacking a core fucose, which affects its biological activities by changing its heparin binding affinity. In human plasma, AT circulates as a mixture of the α-form bearing four oligosaccharides and the β-form lacking an oligosaccharide at Asn135. However, it remains unclear how the immature high-mannose-type oligosaccharides produced by mammalian cells affect biological activities of AT. Here, we succeeded in directly comparing the activities between the high-mannose and complex-types. Interestingly, although there were no substantial differences in thrombin inhibitory activity, the high-mannose-type showed higher heparin binding affinity. The anticoagulant activities were increased by heparin and correlated with the heparin binding affinity, resulting in the strongest anticoagulant activity being displayed in the β-form with the high-mannose-type. In pharmacokinetic profiling, the high-mannose-type showed a much shorter plasma half-life than the complex-type. The β-form was found to have a prolonged plasma half-life compared with the α-form for the high-mannose-type; conversely, the α-form showed a longer half-life than the β-form for the complex-type. The present study highlights that AT physiological activities are strictly controlled not only by a core fucose at the reducing end but also by the high-mannose-type structures at the nonreducing end. The β-form with the immature high-mannose-type appears to function as a more potent anticoagulant than the AT typically found in human plasma, once it emerges in the blood."}

GO-MF

{"project":"GO-MF","denotations":[{"id":"T1","span":{"begin":448,"end":463},"obj":"http://purl.obolibrary.org/obo/GO_0008201"},{"id":"T2","span":{"begin":990,"end":1005},"obj":"http://purl.obolibrary.org/obo/GO_0008201"},{"id":"T3","span":{"begin":1095,"end":1110},"obj":"http://purl.obolibrary.org/obo/GO_0008201"},{"id":"T4","span":{"begin":456,"end":463},"obj":"http://purl.obolibrary.org/obo/GO_0070026"},{"id":"T5","span":{"begin":998,"end":1005},"obj":"http://purl.obolibrary.org/obo/GO_0070026"},{"id":"T6","span":{"begin":1103,"end":1110},"obj":"http://purl.obolibrary.org/obo/GO_0070026"},{"id":"T7","span":{"begin":456,"end":463},"obj":"http://purl.obolibrary.org/obo/GO_0003680"},{"id":"T8","span":{"begin":998,"end":1005},"obj":"http://purl.obolibrary.org/obo/GO_0003680"},{"id":"T9","span":{"begin":1103,"end":1110},"obj":"http://purl.obolibrary.org/obo/GO_0003680"},{"id":"T10","span":{"begin":456,"end":463},"obj":"http://purl.obolibrary.org/obo/GO_0017091"},{"id":"T11","span":{"begin":998,"end":1005},"obj":"http://purl.obolibrary.org/obo/GO_0017091"},{"id":"T12","span":{"begin":1103,"end":1110},"obj":"http://purl.obolibrary.org/obo/GO_0017091"},{"id":"T13","span":{"begin":456,"end":463},"obj":"http://purl.obolibrary.org/obo/GO_0005488"},{"id":"T14","span":{"begin":998,"end":1005},"obj":"http://purl.obolibrary.org/obo/GO_0005488"},{"id":"T15","span":{"begin":1103,"end":1110},"obj":"http://purl.obolibrary.org/obo/GO_0005488"}],"text":"Comparison of biological activities of human antithrombins with high-mannose or complex- type nonfucosylated N-linked oligosaccharides.\nThe structure of the N-linked oligosaccharides attached to antithrombin (AT) has been shown to affect its anticoagulant activity and pharmacokinetics. Human AT has biantennary complex-type oligosaccharides with the unique feature of lacking a core fucose, which affects its biological activities by changing its heparin binding affinity. In human plasma, AT circulates as a mixture of the α-form bearing four oligosaccharides and the β-form lacking an oligosaccharide at Asn135. However, it remains unclear how the immature high-mannose-type oligosaccharides produced by mammalian cells affect biological activities of AT. Here, we succeeded in directly comparing the activities between the high-mannose and complex-types. Interestingly, although there were no substantial differences in thrombin inhibitory activity, the high-mannose-type showed higher heparin binding affinity. The anticoagulant activities were increased by heparin and correlated with the heparin binding affinity, resulting in the strongest anticoagulant activity being displayed in the β-form with the high-mannose-type. In pharmacokinetic profiling, the high-mannose-type showed a much shorter plasma half-life than the complex-type. The β-form was found to have a prolonged plasma half-life compared with the α-form for the high-mannose-type; conversely, the α-form showed a longer half-life than the β-form for the complex-type. The present study highlights that AT physiological activities are strictly controlled not only by a core fucose at the reducing end but also by the high-mannose-type structures at the nonreducing end. The β-form with the immature high-mannose-type appears to function as a more potent anticoagulant than the AT typically found in human plasma, once it emerges in the blood."}

GO-CC

{"project":"GO-CC","denotations":[{"id":"T1","span":{"begin":379,"end":383},"obj":"http://purl.obolibrary.org/obo/GO_0019013"},{"id":"T2","span":{"begin":1640,"end":1644},"obj":"http://purl.obolibrary.org/obo/GO_0019013"},{"id":"T3","span":{"begin":717,"end":722},"obj":"http://purl.obolibrary.org/obo/GO_0005623"}],"text":"Comparison of biological activities of human antithrombins with high-mannose or complex- type nonfucosylated N-linked oligosaccharides.\nThe structure of the N-linked oligosaccharides attached to antithrombin (AT) has been shown to affect its anticoagulant activity and pharmacokinetics. Human AT has biantennary complex-type oligosaccharides with the unique feature of lacking a core fucose, which affects its biological activities by changing its heparin binding affinity. In human plasma, AT circulates as a mixture of the α-form bearing four oligosaccharides and the β-form lacking an oligosaccharide at Asn135. However, it remains unclear how the immature high-mannose-type oligosaccharides produced by mammalian cells affect biological activities of AT. Here, we succeeded in directly comparing the activities between the high-mannose and complex-types. Interestingly, although there were no substantial differences in thrombin inhibitory activity, the high-mannose-type showed higher heparin binding affinity. The anticoagulant activities were increased by heparin and correlated with the heparin binding affinity, resulting in the strongest anticoagulant activity being displayed in the β-form with the high-mannose-type. In pharmacokinetic profiling, the high-mannose-type showed a much shorter plasma half-life than the complex-type. The β-form was found to have a prolonged plasma half-life compared with the α-form for the high-mannose-type; conversely, the α-form showed a longer half-life than the β-form for the complex-type. The present study highlights that AT physiological activities are strictly controlled not only by a core fucose at the reducing end but also by the high-mannose-type structures at the nonreducing end. The β-form with the immature high-mannose-type appears to function as a more potent anticoagulant than the AT typically found in human plasma, once it emerges in the blood."}

UBERON-AE

{"project":"UBERON-AE","denotations":[{"id":"T1","span":{"begin":1907,"end":1912},"obj":"http://purl.obolibrary.org/obo/UBERON_0000178"}],"text":"Comparison of biological activities of human antithrombins with high-mannose or complex- type nonfucosylated N-linked oligosaccharides.\nThe structure of the N-linked oligosaccharides attached to antithrombin (AT) has been shown to affect its anticoagulant activity and pharmacokinetics. Human AT has biantennary complex-type oligosaccharides with the unique feature of lacking a core fucose, which affects its biological activities by changing its heparin binding affinity. In human plasma, AT circulates as a mixture of the α-form bearing four oligosaccharides and the β-form lacking an oligosaccharide at Asn135. However, it remains unclear how the immature high-mannose-type oligosaccharides produced by mammalian cells affect biological activities of AT. Here, we succeeded in directly comparing the activities between the high-mannose and complex-types. Interestingly, although there were no substantial differences in thrombin inhibitory activity, the high-mannose-type showed higher heparin binding affinity. The anticoagulant activities were increased by heparin and correlated with the heparin binding affinity, resulting in the strongest anticoagulant activity being displayed in the β-form with the high-mannose-type. In pharmacokinetic profiling, the high-mannose-type showed a much shorter plasma half-life than the complex-type. The β-form was found to have a prolonged plasma half-life compared with the α-form for the high-mannose-type; conversely, the α-form showed a longer half-life than the β-form for the complex-type. The present study highlights that AT physiological activities are strictly controlled not only by a core fucose at the reducing end but also by the high-mannose-type structures at the nonreducing end. The β-form with the immature high-mannose-type appears to function as a more potent anticoagulant than the AT typically found in human plasma, once it emerges in the blood."}

GlycoBiology-MAT

{"project":"GlycoBiology-MAT","denotations":[{"id":"T1","span":{"begin":1907,"end":1912},"obj":"http://purl.obolibrary.org/obo/MAT_0000315"},{"id":"T2","span":{"begin":1907,"end":1912},"obj":"http://purl.obolibrary.org/obo/MAT_0000083"}],"text":"Comparison of biological activities of human antithrombins with high-mannose or complex- type nonfucosylated N-linked oligosaccharides.\nThe structure of the N-linked oligosaccharides attached to antithrombin (AT) has been shown to affect its anticoagulant activity and pharmacokinetics. Human AT has biantennary complex-type oligosaccharides with the unique feature of lacking a core fucose, which affects its biological activities by changing its heparin binding affinity. In human plasma, AT circulates as a mixture of the α-form bearing four oligosaccharides and the β-form lacking an oligosaccharide at Asn135. However, it remains unclear how the immature high-mannose-type oligosaccharides produced by mammalian cells affect biological activities of AT. Here, we succeeded in directly comparing the activities between the high-mannose and complex-types. Interestingly, although there were no substantial differences in thrombin inhibitory activity, the high-mannose-type showed higher heparin binding affinity. The anticoagulant activities were increased by heparin and correlated with the heparin binding affinity, resulting in the strongest anticoagulant activity being displayed in the β-form with the high-mannose-type. In pharmacokinetic profiling, the high-mannose-type showed a much shorter plasma half-life than the complex-type. The β-form was found to have a prolonged plasma half-life compared with the α-form for the high-mannose-type; conversely, the α-form showed a longer half-life than the β-form for the complex-type. The present study highlights that AT physiological activities are strictly controlled not only by a core fucose at the reducing end but also by the high-mannose-type structures at the nonreducing end. The β-form with the immature high-mannose-type appears to function as a more potent anticoagulant than the AT typically found in human plasma, once it emerges in the blood."}

performance-test

{"project":"performance-test","denotations":[{"id":"PD-UBERON-AE-B_T1","span":{"begin":1907,"end":1912},"obj":"http://purl.obolibrary.org/obo/UBERON_0000178"}],"text":"Comparison of biological activities of human antithrombins with high-mannose or complex- type nonfucosylated N-linked oligosaccharides.\nThe structure of the N-linked oligosaccharides attached to antithrombin (AT) has been shown to affect its anticoagulant activity and pharmacokinetics. Human AT has biantennary complex-type oligosaccharides with the unique feature of lacking a core fucose, which affects its biological activities by changing its heparin binding affinity. In human plasma, AT circulates as a mixture of the α-form bearing four oligosaccharides and the β-form lacking an oligosaccharide at Asn135. However, it remains unclear how the immature high-mannose-type oligosaccharides produced by mammalian cells affect biological activities of AT. Here, we succeeded in directly comparing the activities between the high-mannose and complex-types. Interestingly, although there were no substantial differences in thrombin inhibitory activity, the high-mannose-type showed higher heparin binding affinity. The anticoagulant activities were increased by heparin and correlated with the heparin binding affinity, resulting in the strongest anticoagulant activity being displayed in the β-form with the high-mannose-type. In pharmacokinetic profiling, the high-mannose-type showed a much shorter plasma half-life than the complex-type. The β-form was found to have a prolonged plasma half-life compared with the α-form for the high-mannose-type; conversely, the α-form showed a longer half-life than the β-form for the complex-type. The present study highlights that AT physiological activities are strictly controlled not only by a core fucose at the reducing end but also by the high-mannose-type structures at the nonreducing end. The β-form with the immature high-mannose-type appears to function as a more potent anticoagulant than the AT typically found in human plasma, once it emerges in the blood."}

GlycoBiology-Motifs

{"project":"GlycoBiology-Motifs","denotations":[{"id":"T1","span":{"begin":64,"end":76},"obj":"http://rdf.glycoinfo.org/glycan/G00028MO"},{"id":"T2","span":{"begin":660,"end":672},"obj":"http://rdf.glycoinfo.org/glycan/G00028MO"},{"id":"T3","span":{"begin":827,"end":839},"obj":"http://rdf.glycoinfo.org/glycan/G00028MO"},{"id":"T4","span":{"begin":958,"end":970},"obj":"http://rdf.glycoinfo.org/glycan/G00028MO"},{"id":"T5","span":{"begin":1210,"end":1222},"obj":"http://rdf.glycoinfo.org/glycan/G00028MO"},{"id":"T6","span":{"begin":1263,"end":1275},"obj":"http://rdf.glycoinfo.org/glycan/G00028MO"},{"id":"T7","span":{"begin":1434,"end":1446},"obj":"http://rdf.glycoinfo.org/glycan/G00028MO"},{"id":"T8","span":{"begin":1688,"end":1700},"obj":"http://rdf.glycoinfo.org/glycan/G00028MO"},{"id":"T9","span":{"begin":1770,"end":1782},"obj":"http://rdf.glycoinfo.org/glycan/G00028MO"},{"id":"T10","span":{"begin":448,"end":455},"obj":"http://rdf.glycoinfo.org/glycan/G54161DR"},{"id":"T11","span":{"begin":990,"end":997},"obj":"http://rdf.glycoinfo.org/glycan/G54161DR"},{"id":"T12","span":{"begin":1063,"end":1070},"obj":"http://rdf.glycoinfo.org/glycan/G54161DR"},{"id":"T13","span":{"begin":1095,"end":1102},"obj":"http://rdf.glycoinfo.org/glycan/G54161DR"}],"text":"Comparison of biological activities of human antithrombins with high-mannose or complex- type nonfucosylated N-linked oligosaccharides.\nThe structure of the N-linked oligosaccharides attached to antithrombin (AT) has been shown to affect its anticoagulant activity and pharmacokinetics. Human AT has biantennary complex-type oligosaccharides with the unique feature of lacking a core fucose, which affects its biological activities by changing its heparin binding affinity. In human plasma, AT circulates as a mixture of the α-form bearing four oligosaccharides and the β-form lacking an oligosaccharide at Asn135. However, it remains unclear how the immature high-mannose-type oligosaccharides produced by mammalian cells affect biological activities of AT. Here, we succeeded in directly comparing the activities between the high-mannose and complex-types. Interestingly, although there were no substantial differences in thrombin inhibitory activity, the high-mannose-type showed higher heparin binding affinity. The anticoagulant activities were increased by heparin and correlated with the heparin binding affinity, resulting in the strongest anticoagulant activity being displayed in the β-form with the high-mannose-type. In pharmacokinetic profiling, the high-mannose-type showed a much shorter plasma half-life than the complex-type. The β-form was found to have a prolonged plasma half-life compared with the α-form for the high-mannose-type; conversely, the α-form showed a longer half-life than the β-form for the complex-type. The present study highlights that AT physiological activities are strictly controlled not only by a core fucose at the reducing end but also by the high-mannose-type structures at the nonreducing end. The β-form with the immature high-mannose-type appears to function as a more potent anticoagulant than the AT typically found in human plasma, once it emerges in the blood."}

Anatomy-MAT

{"project":"Anatomy-MAT","denotations":[{"id":"T1","span":{"begin":1907,"end":1912},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"mat_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MAT_0000083"},{"id":"A2","pred":"mat_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MAT_0000315"}],"text":"Comparison of biological activities of human antithrombins with high-mannose or complex- type nonfucosylated N-linked oligosaccharides.\nThe structure of the N-linked oligosaccharides attached to antithrombin (AT) has been shown to affect its anticoagulant activity and pharmacokinetics. Human AT has biantennary complex-type oligosaccharides with the unique feature of lacking a core fucose, which affects its biological activities by changing its heparin binding affinity. In human plasma, AT circulates as a mixture of the α-form bearing four oligosaccharides and the β-form lacking an oligosaccharide at Asn135. However, it remains unclear how the immature high-mannose-type oligosaccharides produced by mammalian cells affect biological activities of AT. Here, we succeeded in directly comparing the activities between the high-mannose and complex-types. Interestingly, although there were no substantial differences in thrombin inhibitory activity, the high-mannose-type showed higher heparin binding affinity. The anticoagulant activities were increased by heparin and correlated with the heparin binding affinity, resulting in the strongest anticoagulant activity being displayed in the β-form with the high-mannose-type. In pharmacokinetic profiling, the high-mannose-type showed a much shorter plasma half-life than the complex-type. The β-form was found to have a prolonged plasma half-life compared with the α-form for the high-mannose-type; conversely, the α-form showed a longer half-life than the β-form for the complex-type. The present study highlights that AT physiological activities are strictly controlled not only by a core fucose at the reducing end but also by the high-mannose-type structures at the nonreducing end. The β-form with the immature high-mannose-type appears to function as a more potent anticoagulant than the AT typically found in human plasma, once it emerges in the blood."}

NCBITAXON

{"project":"NCBITAXON","denotations":[{"id":"T1","span":{"begin":39,"end":44},"obj":"OrganismTaxon"},{"id":"T2","span":{"begin":287,"end":292},"obj":"OrganismTaxon"},{"id":"T3","span":{"begin":477,"end":482},"obj":"OrganismTaxon"},{"id":"T4","span":{"begin":1870,"end":1875},"obj":"OrganismTaxon"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"9606"},{"id":"A2","pred":"db_id","subj":"T2","obj":"9606"},{"id":"A3","pred":"db_id","subj":"T3","obj":"9606"},{"id":"A4","pred":"db_id","subj":"T4","obj":"9606"}],"text":"Comparison of biological activities of human antithrombins with high-mannose or complex- type nonfucosylated N-linked oligosaccharides.\nThe structure of the N-linked oligosaccharides attached to antithrombin (AT) has been shown to affect its anticoagulant activity and pharmacokinetics. Human AT has biantennary complex-type oligosaccharides with the unique feature of lacking a core fucose, which affects its biological activities by changing its heparin binding affinity. In human plasma, AT circulates as a mixture of the α-form bearing four oligosaccharides and the β-form lacking an oligosaccharide at Asn135. However, it remains unclear how the immature high-mannose-type oligosaccharides produced by mammalian cells affect biological activities of AT. Here, we succeeded in directly comparing the activities between the high-mannose and complex-types. Interestingly, although there were no substantial differences in thrombin inhibitory activity, the high-mannose-type showed higher heparin binding affinity. The anticoagulant activities were increased by heparin and correlated with the heparin binding affinity, resulting in the strongest anticoagulant activity being displayed in the β-form with the high-mannose-type. In pharmacokinetic profiling, the high-mannose-type showed a much shorter plasma half-life than the complex-type. The β-form was found to have a prolonged plasma half-life compared with the α-form for the high-mannose-type; conversely, the α-form showed a longer half-life than the β-form for the complex-type. The present study highlights that AT physiological activities are strictly controlled not only by a core fucose at the reducing end but also by the high-mannose-type structures at the nonreducing end. The β-form with the immature high-mannose-type appears to function as a more potent anticoagulant than the AT typically found in human plasma, once it emerges in the blood."}

Anatomy-UBERON

{"project":"Anatomy-UBERON","denotations":[{"id":"T1","span":{"begin":483,"end":489},"obj":"Body_part"},{"id":"T2","span":{"begin":1303,"end":1309},"obj":"Body_part"},{"id":"T3","span":{"begin":1384,"end":1390},"obj":"Body_part"},{"id":"T4","span":{"begin":1876,"end":1882},"obj":"Body_part"},{"id":"T5","span":{"begin":1907,"end":1912},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_0001969"},{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/UBERON_0001969"},{"id":"A3","pred":"uberon_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/UBERON_0001969"},{"id":"A4","pred":"uberon_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/UBERON_0001969"},{"id":"A5","pred":"uberon_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/UBERON_0000178"}],"text":"Comparison of biological activities of human antithrombins with high-mannose or complex- type nonfucosylated N-linked oligosaccharides.\nThe structure of the N-linked oligosaccharides attached to antithrombin (AT) has been shown to affect its anticoagulant activity and pharmacokinetics. Human AT has biantennary complex-type oligosaccharides with the unique feature of lacking a core fucose, which affects its biological activities by changing its heparin binding affinity. In human plasma, AT circulates as a mixture of the α-form bearing four oligosaccharides and the β-form lacking an oligosaccharide at Asn135. However, it remains unclear how the immature high-mannose-type oligosaccharides produced by mammalian cells affect biological activities of AT. Here, we succeeded in directly comparing the activities between the high-mannose and complex-types. Interestingly, although there were no substantial differences in thrombin inhibitory activity, the high-mannose-type showed higher heparin binding affinity. The anticoagulant activities were increased by heparin and correlated with the heparin binding affinity, resulting in the strongest anticoagulant activity being displayed in the β-form with the high-mannose-type. In pharmacokinetic profiling, the high-mannose-type showed a much shorter plasma half-life than the complex-type. The β-form was found to have a prolonged plasma half-life compared with the α-form for the high-mannose-type; conversely, the α-form showed a longer half-life than the β-form for the complex-type. The present study highlights that AT physiological activities are strictly controlled not only by a core fucose at the reducing end but also by the high-mannose-type structures at the nonreducing end. The β-form with the immature high-mannose-type appears to function as a more potent anticoagulant than the AT typically found in human plasma, once it emerges in the blood."}