Pegvisomant: structure and function.
Pegvisomant is the pegylated form of mutant growth hormone (B2036). B2036 has increased affinity in one binding site and lowered affinity in its second binding site, it has been shown that this molecule still enables dimerisation of the growth hormone receptor at the cell surface but does not allow the necessary conformational changes for signalling. Pegylation decreases the antagonistic activity of B2036, however the rate of clearance of the pegylated B2036 is greatly reduced compared to the unpegylated form. Even though the antagonistic activity of pegvisomant is lower than B2036, the reduced rate of clearance makes it an effective clinical drug for the treatment of conditions such as acromegaly.
Division of Clinical Sciences, University of Sheffield, Northern General Hospital, Sheffield S5 7AU, UK.
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Pradhananga
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Wilkinson
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Ross
D001665:Binding Sites; D019382:Human Growth Hormone / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D013329:Structure-Activity Relationship
D019382:Human Growth Hormone; C406545:pegvisomant