Issue 33, 2017

Effect of trehalose polymer regioisomers on protein stabilization

Abstract

There is considerable interest in the use of proteins as therapeutics and as chemical and biochemical reagents. However, many proteins are unstable and aggregate when exposed to stressors, including increased temperature, pH change, agitation, and desiccation. Polymers with side chain trehalose units were shown to be effective protein stabilizers, preventing aggregation and prolonging activity. Herein, we report the synthesis and characterization of four trehalose regioisomers containing a vinylbenzyl ether moiety at either the 2-O, 3-O, 4-O, or 6-O position. Computational analysis of these regioisomers suggested that they differ in their conformational flexibility, but all retained the native clam shell conformation of trehalose. Polymers were synthesized from the monomers separately via free radical polymerization and one polymer was prepared containing all of the regioisomers. The polymers were tested for their ability to stabilize insulin, and were found to prevent agitation-induced aggregation comparably. The results show that for insulin the effect of trehalose positional modification is minimal and suggest that the clam shell conformation itself may be more important than the polymer backbone attachment site for stabilization of proteins.

Graphical abstract: Effect of trehalose polymer regioisomers on protein stabilization

Supplementary files

Article information

Article type
Paper
Submitted
25 Agd 2017
Accepted
25 Qas 2017
First published
03 Qad 2017

Polym. Chem., 2017,8, 4781-4788

Effect of trehalose polymer regioisomers on protein stabilization

M. S. Messina, J. H. Ko, Z. Yang, M. J. Strouse, K. N. Houk and H. D. Maynard, Polym. Chem., 2017, 8, 4781 DOI: 10.1039/C7PY00700K

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements