An efficient methodology to introduce o-(aminomethyl)phenyl-boronic acids into peptides: alkylation of secondary amines. (28th November 2016)

• Record Type: Journal Article
• Authors: Hernandez, Erik T.; Kolesnichenko, Igor V.; Reuther, James F.; Anslyn, Eric V.
• Is Part Of: New journal of chemistry. Volume 41:Number 1(2017)
• Page Start: 126
• Page End: 133
• Publication Date: 2016-11-28
• Subjects: Chemistry -- Periodicals; Chimie -- Périodiques; 540
• DOI: 10.1039/c6nj02862d
• Languages: English
• ISSNs: 1144-0546

Abstract

Abstract : Three synthetically accessible approaches were developed to make complex multi-boronic acid peptides. Abstract : Current approaches for incorporating boronic acids into peptides require one of the following: the synthesis of commercially unavailable pinacol-protected boronate ester amino acid building blocks, amidation of small-molecule amine-containing boronic acids, or reductive amination of amine residues with 2-formylphenyl boronic acid. These methods have drawbacks, such as the use of excess starting materials, the lack of reactive-site specificity, or the inability to add multiple boronic acids in solution. In addition, several of these approaches do not allow for incorporation of the critical o -aminomethyl functionality that allows for binding of saccharides under physiological conditions. In this work, we report three methods to functionalize synthetic peptides with boronic acids using solid-phase and solution-phase chemistries by alkylating a secondary amine with o -(bromomethyl)phenylboronic acid. Solution-phase chemistries afforded the highest yields, and were used to synthesize seven complex biotinylated multi-boronic acid peptides.