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PMC:7795856 / 16963-18919 JSONTXT

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LitCovid-PubTator

Id Subject Object Predicate Lexical cue tao:has_database_id
302 52-55 Gene denotes Tα1 Gene:134864
303 426-439 Gene denotes serum albumin Gene:213
304 504-507 Gene denotes Tα1 Gene:134864
305 790-793 Gene denotes Tα1 Gene:134864
306 1597-1600 Gene denotes Tα1 Gene:134864
307 1710-1713 Gene denotes Tα1 Gene:134864
308 1842-1845 Gene denotes Tα1 Gene:134864
309 222-226 Species denotes rats Tax:10116
310 420-425 Species denotes human Tax:9606
311 18-21 Chemical denotes PAS
312 276-283 Chemical denotes Tα1-PAS
313 698-732 Chemical denotes arginylglycylaspartic acid peptide
314 605-610 Disease denotes tumor MESH:D009369
315 1634-1640 Disease denotes cancer MESH:D009369

LitCovid-PD-HP

Id Subject Object Predicate Lexical cue hp_id
T15 605-610 Phenotype denotes tumor http://purl.obolibrary.org/obo/HP_0002664
T16 1634-1640 Phenotype denotes cancer http://purl.obolibrary.org/obo/HP_0002664

LitCovid-sentences

Id Subject Object Predicate Lexical cue
T100 0-149 Sentence denotes Attachment of the PAS sequence at either end of the Tα1 peptide increased the hydrodynamic volume by more than an order of magnitude as shown by SEC.
T101 150-376 Sentence denotes This strongly expanded molecular size resulted in a plasma half-life in rats of around 16 h after a subcutaneous injection of Tα1-PAS, which is more than an 8-fold increase compared to the unmodified peptide drug (1.9 h) [41].
T102 377-574 Sentence denotes Based on in vitro cell culture assays with human serum albumin fusion proteins [49], both the C-terminus and the N-terminus of Tα1 should be permissible to modification while retaining bioactivity.
T103 575-765 Sentence denotes This was also shown in animal tumor models for C-terminal fusion with an immunoglobulin Fc fragment [41], an internalizing arginylglycylaspartic acid peptide iRGD [50], and thymopentin [51].
T104 766-1013 Sentence denotes However, in the case of Tα1, some caution is appropriate regarding the significance of in vitro cell culture assays as its mode of action is complex and involves different receptors provoking multiple biological effects on various cell types [52].
T105 1014-1206 Sentence denotes Second, a prolonged circulation in the body as demonstrated here via application of the PASylation technology influences both binding kinetics and bioactivity, which is not reflected in vitro.
T106 1207-1581 Sentence denotes While attachment of large macromolecules, such as PAS polypeptides or albumin, but also PEG [53], can lead to lower receptor association rates for bioactive peptides or proteins, this is usually overcompensated by the drastically prolonged in vivo half-life, which results in a strongly enhanced bioactivity as demonstrated for multiple PASylated biopharmaceuticals [37,54].
T107 1582-1740 Sentence denotes In the case of Tα1, superior effects in preclinical cancer models due to prolonged circulation were recently demonstrated for a Tα1-Fc fusion protein [41,44].
T108 1741-1956 Sentence denotes Such studies would be the obvious next step to investigate enhanced in vivo bioactivity of PASylated Tα1, and it will be interesting to see whether its N-terminally or C-terminally PASylated version performs better.