Long-Acting Human Growth Hormone Analogue by Noncovalent Albumin Binding

Bioconjugate Chemistry
Henrik S Ramírez-AndersenNils L Johansen

Abstract

The present work describes a series of human growth hormone (hGH) albumin binder conjugates with an extended in vivo half-life. A broad range of different conjugates were studied by varying the albumin binder structure and conjugation site. Conjugates were conveniently obtained by reductive alkylation or by alkylation to introduced cysteines using functionalized albumin-binding side chains. In vitro and in vivo profiling provided the basis for identification of position L101C in human growth hormone as the most optimal position for conjugation, where both a sufficient level of receptor binding and a suitably long half-life could yield a molecule with potential for a once-weekly dosing regimen.

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Citations

Jun 11, 2019·Endocrine Reviews·Richard I G Holt, Ken K Y Ho
Apr 24, 2019·The Journal of Pharmacology and Experimental Therapeutics·A R Satvik IyengarAbhay H Pande
Sep 10, 2019·Expert Opinion on Drug Delivery·Sadia SikderDhananjay Pal
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Dec 24, 2018·Journal of Controlled Release : Official Journal of the Controlled Release Society·Romel Menacho-MelgarMichael D Lynch

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