Campus Units

Chemistry

Document Type

Article

Publication Version

Accepted Manuscript

Publication Date

4-18-2018

Journal or Book Title

Bioconjugate Chemistry

Volume

29

Issue

4

First Page

1438

Last Page

1445

DOI

10.1021/acs.bioconjchem.8b00121

Abstract

Folate receptors are overexpressed on cancer cells and frequently used for targeted delivery. Creation of synthetic receptors to bind folic acid and its analogues in water, however, is challenging because of its complex hydrogen-bonding patterns and competition for hydrogen bonds from the solvent. Micellar imprinting within cross-linkable surfactants circumvented these problems because the nonpolar micellar environment strengthened the hydrogen bonds between the amide group in the surfactant and the template molecule. Incorporation of polymerizable thiouronium functional monomers further enhanced the binding through hydrogen-bond-reinforced ion pairs with the glutamate moiety of the template. The resulting imprinted micelles were able to bind folate and their analogues with submicromolar affinity and distinguish small changes in the hydrogen-bonding patterns as well as the number/position of carboxylic acids. The binding constant obtained was 2–3 orders of magnitude higher than those reported for small-molecule synthetic receptors. Our binding study also revealed interesting details in the binding. For example, the relative contributions of different segments of the molecule to the binding followed the order of carboxylates > pyrimidine ring > pyrazine ring.

Comments

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Bioconjugate Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see DOI: 10.1021/acs.bioconjchem.8b00121. Posted with permission.

Copyright Owner

American Chemical Society

Language

en

File Format

application/pdf

Published Version

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