PubMed:10593387 JSONTXT

{"project":"bionlp-st-epi-2011-training","denotations":[{"id":"T1","span":{"begin":416,"end":418},"obj":"Protein"},{"id":"T2","span":{"begin":423,"end":436},"obj":"Protein"},{"id":"T3","span":{"begin":832,"end":834},"obj":"Protein"},{"id":"T4","span":{"begin":838,"end":851},"obj":"Protein"}],"text":"Deglycosylation of a bifunctional lutropin-follitropin agonist reduced its follitropin activity more than its lutropin activity.\nOBJECTIVE: To design a drug that blocks the gonadal actions of lutropins and follitropins.\nDESIGN: Controlled in vitro study.\nSETTING: Academic laboratory.\nPATIENT(S): None.\nINTERVENTION(S): We removed three glycosylation signals from an hCG-hFSH chimera known to have high affinity for LH and FSH receptors, expecting this would create a bifunctional antagonist (dgCFC). To offset the inhibition of subunit combination caused by deglycosylation of alpha-subunit loop 2, we prepared dgCFC as a single-chain fusion protein containing the alpha-subunit downstream of the chimeric beta-subunit.\nMAIN OUTCOME MEASURE(S): Receptor binding, cyclic adenosine monophosphate accumulation.\nRESULT(S): dgCFC bound LH or FSH receptors similar to hCG or hFSH. It was a partial agonist and had one tenth the efficacy of hFSH and two thirds the efficacy of hCG.\nCONCLUSION(S): The surprising high residual lutropin activity of dgCFC indicated that its FSH residues offset the effects of deglycosylation, suggesting this approach to preparing a bifunctional antagonist is unlikely to lead to a useful drug. The increased lutropin efficacy of dgCFC relative to deglycosylated hCG supports the idea that oligosaccharides modulate glycoprotein hormone efficacy through an influence on hormone conformation."}