Jump to main content
Jump to site search

Issue 23, 2016
Previous Article Next Article

Synthesis and amylin receptor activity of glycomimetics of pramlintide using click chemistry

Author affiliations

Abstract

Pramlintide (Symlin®), a synthetic analogue of the neuroendocrine hormone amylin, is devoid of the tendency to form cytotoxic amyloid fibrils and is currently used in patients with type I and type II diabetes mellitus as an adjunctive therapy with insulin or insulin analogues. As part of an on-going search for a pramlintide analogue with improved pharmacokinetic properties, we herein report the synthesis of mono- and di-glycosylated analogues of pramlintide and their activity at the AMY1(a) receptor. Introduction of N-glycosylated amino acids into the pramlintide sequence afforded the native N-linked glycomimetics whilst use of Cu(I)-catalysed azide–alkyne 1,3-dipolar cycloaddition (click) chemistry delivered 1,2,3-triazole linked glycomimetics. AMY1(a) receptor activity was retained by incorporation of single or multiple GlcNAc moieties at positions 21 and 35 of native pramlintide. Importantly, no difference in AMY1(a) activity was observed between native N-linked glycomimetics and 1,2,3-triazole linked glycomimetics demonstrating that the click variants can act as surrogates for the native N-glycosides in a biological setting.

Graphical abstract: Synthesis and amylin receptor activity of glycomimetics of pramlintide using click chemistry

Back to tab navigation

Supplementary files

Publication details

The article was received on 03 Mar 2016, accepted on 21 Apr 2016 and first published on 26 Apr 2016


Article type: Paper
DOI: 10.1039/C6OB00850J
Citation: Org. Biomol. Chem., 2016,14, 5238-5245
  •   Request permissions

    Synthesis and amylin receptor activity of glycomimetics of pramlintide using click chemistry

    L. R. Yule, R. L. Bower, H. Kaur, R. Kowalczyk, D. L. Hay and Margaret. A. Brimble, Org. Biomol. Chem., 2016, 14, 5238
    DOI: 10.1039/C6OB00850J

Search articles by author

Spotlight

Advertisements