Issue 9, 2017

Heterocyclic boronic acids display sialic acid selective binding in a hypoxic tumor relevant acidic environment

Abstract

Boronic acids are well known for their ability to reversibly interact with the diol groups found in sugars and glycoproteins. However, they are generally indiscriminate in their binding. Herein we describe the discovery of a group of heterocyclic boronic acids demonstrating unusually high affinity and selectivity for sialic acids (SAs or N-acetylneuraminic acid), which are sugar residues that are intimately linked with tumor growth and cancer progression. Remarkably, these interactions strengthen under the weakly acidic pH conditions associated with a hypoxic tumoral microenvironment. In vitro competitive binding assays uncovered a significantly higher ability of 5-boronopicolinic acid, one of the derivatives identified in this work as a strong SA-binder, to interact with cell surface SA in comparison to a gold-standard structure, 3-propionamidophenylboronic acid, which has proven to be an efficient SA-binder in numerous reports. This structure also proved to be suitable for further chemical conjugation with a well-preserved SA-binding capability. These findings suggest an attractive alternative to other ongoing boronic acid based chemistry techniques aiming to achieve tumor-specific chemotherapies and diagnoses.

Graphical abstract: Heterocyclic boronic acids display sialic acid selective binding in a hypoxic tumor relevant acidic environment

Supplementary files

Article information

Article type
Edge Article
Submitted
28 Apr 2017
Accepted
19 Jun 2017
First published
05 Jul 2017
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2017,8, 6165-6170

Heterocyclic boronic acids display sialic acid selective binding in a hypoxic tumor relevant acidic environment

A. Matsumoto, A. J. Stephenson-Brown, T. Khan, T. Miyazawa, H. Cabral, K. Kataoka and Y. Miyahara, Chem. Sci., 2017, 8, 6165 DOI: 10.1039/C7SC01905J

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