Merging the Versatile Functionalities of Boronic Acid with Peptides

Abstract

Peptides inherently feature the favorable properties of being easily synthesized, water-soluble, biocompatible, and typically non-toxic. Thus, boronic acid has been widely integrated with peptides with the goal of discovering peptide ligands with novel biological activities, and this effort has led to broad applications. Taking the integration between boronic acid and peptide as a starting point, we provide an overview of the latest research advances and highlight the versatile and robust functionalities of boronic acid. In this review, we summarize the diverse applications of peptide boronic acids in medicinal chemistry and chemical biology, including the identification of covalent reversible enzyme inhibitors, recognition, and detection of glycans on proteins or cancer cell surface, delivery of siRNAs, development of pH responsive devices, and recognition of RNA or bacterial surfaces. Additionally, we discuss boronic acid-mediated peptide cyclization and peptide modifications, as well as the facile chemical synthesis of peptide boronic acids, which paved the way for developing a growing number of peptide boronic acids.

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

“…The merging field of boron chemistry with peptide has been versatile, adaptable applications in medicinal chemistry 12,69 and bioconjugation 15 . Hence, we projected utilizing this borono peptide preparation method and modulating them to gain ample opportunities in the biomedical arena through conjugation, cyclization, boron-derivative modification, and glycan recognition.…”

The Zinc-Binding Group Effect: Lessons from Non-Hydroxamic Acid Vorinostat Analogs

“…107,108 Hence, this functional group has drawn considerable attention from medicinal chemists. 109 The use of boronic acid as a chelator of active-site metals to induce inhibition of the enzyme of interest seems to be studied to a lesser extent, but was done for metallo-β-lactamases, coordinating zinc and acting as tetrahedral intermediate, which proved to be successful. 110 The acidity of boronic acid is influenced by the substituent attached to the boron atom, with a pK a ranging from 4 to 10 in water.…”

“…The introduction of a boronic acid functionality in bioactive molecules has been demonstrated to improve selectivity, physicochemical and PK properties, and activity. − It is a strong Lewis acid, despite the presence of two hydroxy groups, owing to the empty p-orbital of the sp 2 -hybridized boron atom (Figure ). This enables boronic acid compounds to form reversible covalent bonds with amino acids, a trait exploited by the blockbuster drug Bortezomib for the treatment of the hematological cancer multiple myeloma. , In addition, boronic acid is also able to bind diol units as present in saccharides and is considered to be a bioisostere for carboxylic acids in drug design. , Hence, this functional group has drawn considerable attention from medicinal chemists . The use of boronic acid as a chelator of active-site metals to induce inhibition of the enzyme of interest seems to be studied to a lesser extent, but was done for metallo-β-lactamases, coordinating zinc and acting as tetrahedral intermediate, which proved to be successful …”

New luminescent organoboron esters based on damnacanthal: one-pot multicomponent synthesis, optical behavior, cytotoxicity, and selectivity studies against MDA-MBA-231 breast cancer cells

“…Over the past years, the development of biogenic templates based on α-amino acids, 1 peptides, 2 sugar analogues, 3,4 DNA fragments, 5 steroids, 6 and bioactive metabolites 7 coordinated to transition metal, 8 noble metal 9 and main group elements 10–12 has gained increasing attention as they can give access to many bio-organometallic compounds with promising applications like therapeutic agents 13 and fluorescent probes. 14 Among these compounds, plant-synthesized anthraquinones are a versatile type of chemical scaffold with multiple therapeutic applications, whose planarity, rigidity, and aromaticity allow them to act as DNA intercalators.…”