The Synthesis of Alkyne-human Relaxin-2 for Labeling with Different Azido Molecules by Click Chemistry

摘要

Human relaxin-2 is a member of insulin super family, which is expressed in placenta, deciduas, prostate and plays a vital role in pregnancy, aging, fibrosis, cardioprotection, inflammation, vasodilation and preeclampsia. It has recently been completed successful Phase III clinical trials for the treatment of acute heart failure. Due to non-specific binding, it is very challenging to label human relaxin-2 with small molecules such as fluorescent dyes, biotin etc by activated esters. In order to solve this problem, we designed a human relaxin-2 analogue (alkyne-human relaxin) which has a propargyl-Gly at the N-terminal of B-chain of human relaxin-2. This allows attachment of functionalized small molecules via click chemistry. It was prepared by SPPS followed by regioselective disulfide formation. We describe its preparation and the use of Cy5.5-azide and PEG5000-azide for labeling the alkyne-human relaxin-2 by click chemistry.