Jump to main content
Jump to site search

Issue 41, 2018
Previous Article Next Article

Facile saccharide-free mimetics that recapitulate key features of glycosaminoglycan sulfation patterns

Author affiliations

Abstract

Controlling glycosaminoglycan (GAG) activity to exploit its immense potential in biology ultimately requires facile manipulation of sulfation patterns associated with GAGs. However, satisfying this requirement in full remains challenging, given that synthesis of GAGs is technically arduous while convenient GAG mimetics often produce sulfation patterns that are uncharacteristic of GAGs. To overcome this, we develop saccharide-free polyproline-based GAG mimetics (PGMs) that can be facilely assembled via amide coupling chemistry. Molecular dynamics simulations show that PGMs recapitulate key GAG structural features (i.e. ∼9 Å-sized repeating units, periodicity and helicity) and as with GAGs, can be tuned to introduce systematic variations in sulfate clustering and spacing. Functionally, a variety of PGMs control various GAG activities (concerning P-selectin, neurotrophic factors and heparinase) and exhibit GAG-like characteristics such as progressive modulation, comparable effectiveness with heparins, need for different sequences to suit different activities and the presence of a “minimal bioactive length”. Furthermore, PGMs produce consistent effects in vivo and successfully provide therapeutic benefits over cancer metastasis. Taken together with their high level of biosafety, PGMs answer the long-standing need for an effective and practicable strategy to manipulate GAG-appropriate sulfation patterns and exploit GAG activity in medicine and biotechnology.

Graphical abstract: Facile saccharide-free mimetics that recapitulate key features of glycosaminoglycan sulfation patterns

Back to tab navigation

Supplementary files

Article information


Submitted
25 May 2018
Accepted
21 Aug 2018
First published
24 Aug 2018

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2018,9, 7940-7947
Article type
Edge Article

Facile saccharide-free mimetics that recapitulate key features of glycosaminoglycan sulfation patterns

T. C. Lim, S. Cai, R. G. Huber, P. J. Bond, P. X. Siew Chia, S. L. Khou, S. Gao, S. S. Lee and S. Lee, Chem. Sci., 2018, 9, 7940 DOI: 10.1039/C8SC02303D

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

Read more about how to correctly acknowledge RSC content.


Social activity

Search articles by author

Spotlight

Advertisements