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, Y. Miyahara

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)6165-6170
Number of pages6
JournalChemical Science
Issue number9
Publication statusPublished - 2017


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