Synthesis of multivalent polymer-aptamer conjugates with enhanced inhibitory potency

International Journal of Nanomedicine
Jacob T MartinRavi S Kane

Abstract

We are interested in designing a modular strategy for creating potent multivalent ligands, which frequently can be used as effective inhibitors of undesired biomolecular interactions. For example, such inhibitors might prevent the self-assembly of bacterial toxins or the attachment of a virus to its host cell receptors. We used a biocompatible polyamino acid polymer as a scaffold for grafting multiple copies of an oligonucleotide aptamer (OA). Specifically, the carboxylates on the side chains of polyglutamic acid (PGA) were modified with a thiol-reactive linker, N-aminoethyl maleimide (AEM), and thiol-functionalized OAs were attached to the maleimide moieties. The resulting conjugates were tested for their ability to compete with and inhibit the binding of unconjugated monovalent OAs to the target cell receptor. Multivalent PGA-OA conjugates with low, medium, and high valency were successfully prepared. The varying valency and successful purification to remove unconjugated OAs were confirmed by polyacrylamide gel electrophoresis. The resulting purified conjugates inhibited the binding of unconjugated monovalent OAs, and the measured half maximal inhibitory concentration (IC50) values corresponded to a 38-88-fold enhancement of ...Continue Reading

Citations

Oct 24, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Eun-Hye KimJun Akimoto
May 1, 2021·Pharmaceuticals·Frank H T NelissenHans A Heus

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Methods Mentioned

BETA
electrophoresis
size-exclusion chromatography
flow cytometry

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