Capturing sialyl-glycan via a site-selective installation of boronic acid repertoire in peptides

19 May 2022, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

The broad spectrum of covalent binding modes and interactions has ‘magically’ popularized the submission of boronic acid-mediated chemistry into chemical biology and medicinal chemistry. Since borono peptide-based applications are emerging, simplistic methods for direct late-stage and site-selective installation of a versatile boronic acid (BA) repertoire onto peptides are desirable, given the limited chemical strategies. Here, we investigate the efficacy of thiol-ene click chemistry for installing functionally versatile BA derivatives on numerous bioactive, native peptides in a site-selective manner. The work emphasizes adaptable applications with BA-modified peptides, such as cyclization, conjugation, and biomolecule recognition. To this end, the click method enables us to nurture the sialyl-glycans binding aptitude of various BA-modified WGA peptides concurrently. The consequence reveals that the WGA peptide (in silico derived from wheat germ agglutinin), which shows a considerably low affinity to sialic acid, turns into a potent and selective binder in the attendance of a suitable BA probe to it. The synergistic recognition intensified the binding and profiling of sialyl-glycan on cancer cell lines compared with widely used lectin, Sambucus nigra.

Keywords

Thiol-ene click
Boronic acid
Peptide modification
Sialyl-glycan
Cancer recognition.

Supplementary materials

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Title
Capturing sialyl-glycan via a site-selective installation of boronic acid repertoire in peptides
Description
This contribution explores the compatibility and efficacy of radical-mediated thiol-ene ‘click’ reaction for the installation of popular BA repertoire onto synthetically programmed cysteine (Cys) residue(s) in biologically active peptides. These synthetic boronopeptides reveal a multitude of reactivity to peptide cyclization, conjugation, derivatization, and selective sialyl-glycan recognition. Furthermore, we studied the synergistic binding modulation abilities of WGA (wheat germ agglutinin, 62-73) peptide to sialyl-glycan when chemically distinct BA derivatives were installed on it. In silico understanding of WGA peptide interaction with sialyl-glycan, quantitative analysis of cancer cells’ staining ability through FACS, selectivity studies, and NMR binding studies are the key techniques used to develop the borono-peptide probe that can be further improved in clinical imaging.
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