Jump to main content
Jump to site search

Issue 41, 2014
Previous Article Next Article

Convergent chemoenzymatic synthesis of a library of glycosylated analogues of pramlintide: structure–activity relationships for amylin receptor agonism

Author affiliations

Abstract

Pramlintide (Symlin®), a synthetic analogue of the naturally occurring pancreatic hormone amylin, is currently used with insulin in adjunctive therapy for type 1 and type 2 diabetes mellitus. Herein we report a systematic study into the effect that N-glycosylation of pramlintide has on activation of amylin receptors. A highly efficient convergent synthetic route, involving a combination of solid phase peptide synthesis and enzymatic glycosylation, delivered a library of N-glycosylated variants of pramlintide bearing either GlcNAc, the core N-glycan pentasaccharide [Man3(GlcNAc)2] or a complex biantennary glycan [(NeuAcGalGlcNAcMan)2Man(GlcNAc)2] at each of its six asparagine residues. The majority of glycosylated versions of pramlintide were potent receptor agonists, suggesting that N-glycosylation may be used as a tool to optimise the pharmacokinetic properties of pramlintide and so deliver improved therapeutic agents for the treatment of diabetes and obesity.

Graphical abstract: Convergent chemoenzymatic synthesis of a library of glycosylated analogues of pramlintide: structure–activity relationships for amylin receptor agonism

Back to tab navigation

Supplementary files

Publication details

The article was received on 11 Jun 2014, accepted on 10 Jul 2014 and first published on 10 Jul 2014


Article type: Paper
DOI: 10.1039/C4OB01208A
Author version available: Download Author version (PDF)
Citation: Org. Biomol. Chem., 2014,12, 8142-8151
  •   Request permissions

    Convergent chemoenzymatic synthesis of a library of glycosylated analogues of pramlintide: structure–activity relationships for amylin receptor agonism

    R. Kowalczyk, M. A. Brimble, Y. Tomabechi, A. J. Fairbanks, M. Fletcher and D. L. Hay, Org. Biomol. Chem., 2014, 12, 8142
    DOI: 10.1039/C4OB01208A

Search articles by author

Spotlight

Advertisements