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Drug mimic induced conformational changes in model polymer-drug conjugates characterized by small-angle neutron scattering

Paul, Alison, James, Craig, Heenan, Richard K. and Schweins, Ralf 2010. Drug mimic induced conformational changes in model polymer-drug conjugates characterized by small-angle neutron scattering. Biomacromolecules 11 (8) , pp. 1978-1982. 10.1021/bm1003338

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Abstract

Copolymers based on poly(N-(2-hydroxypropylmethacrylamide)) with conjugated Doxrubicin are established as candidate anticancer therapeutics. Two HPMA-co-polymers (ca. 35000 g mol−1) with 2.5 and 8 mol % gly-phe-leu-gly peptidyl side-chain content have been modified using linear hydrocarbon and small aromatic molecules as simple drug mimics. This first contrast-variation SANS study on these systems demonstrates, combined with detailed modeling, a controlled switch from random coil to a more defined morphology induced by inclusion of a series of model drug mimics. Relatively small changes in drug-mimic type and loading can significantly alter the solution conformation, and we tentatively propose a helical type structure that is more or less tightly wound, depending on both hydrophobe loading and type. The results presented have important implications for understanding the influence of conjugate structure on solution properties, which is an important factor influencing biological and clinical activity.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Chemistry
Subjects: Q Science > QD Chemistry
Publisher: American Chemical Society
ISSN: 1525-7797
Last Modified: 04 Jun 2017 02:57
URI: http://orca-mwe.cf.ac.uk/id/eprint/14582

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