Synthesis of isotopically labelled αCGRP8‐37 and its lipidated analogue

Lipidated αCGRP8 ‐37 and native αCGRP8 ‐37 are peptide antagonists of the CGRP receptor and are consequently suspected to possess antimigraine properties.13C and15N isotopically labelled variants of lipidated αCGRP8 ‐37 and native αCGRP8 ‐37 were prepared using an Fmoc solid phase peptide synthesis strategy for the purpose of the half ‐life determination.13C and15N labelled amino acids could be installed using a significantly reduced molar equivalence of activating agent and base compared to normal, whilst maintaining good coupling efficiency. α‐Calcitonin gene related peptide (αCGRP) inhibitors are important medicinal targets due to their ability to produce antimigraine effects, thus, the discovery of long‐acting αCGRP inhibitors is of significant interest. Herein we report the synthesis of an isotopically labelled version of the well‐known CGRP receptor antagonist, αCGRP8 ‐37, as well as lipidated αCGRP8 ‐37 with comparable antagonistic activity. These isotopically labelled peptides can be employed in assays to determine the metabolic stability of the lipidated αCGRP8 ‐37 and compare this with the stability of known αCGRP8 ‐37.

Source: Journal of Labelled Compounds and Radiopharmaceuticals - March 26, 2020 Category: Biochemistry Authors: Benjamin L. Lu, Kerry M. Loomes, Debbie L. Hay, Paul W.R. Harris, Margaret A. Brimble Tags: RESEARCH ARTICLE Source Type: research