Chemistry

Challenges and Strategies for Synthesizing Glutamyl Hydrazide Containing Peptides

Document Type

Article

Abstract

Herein, we detail several specific challenges that hinder the effective synthesis of glutamyl hydrazide containing peptides, and we describe a synthetic strategy to work around these challenges. Glutamyl hydrazide is an unnatural amino acid residue that bears an acyl hydrazide functional group on its side chain. This family of compounds has the potential to provide potent and selective inhibitor molecules for several families of enzymes. During peptide synthesis, however, these side chains-even in protected form-can derail the synthesis by initiating undesired side reactions. Avoiding these side reactions is critical for enabling effective access to this family of compounds. © 2022. Thieme. All rights reserved.

Funding for this work was provided by Clark University. N.S.M. acknowledges a Gustaf H. Carlson Summer Research Fellowship. S.I. acknowledges a summer fellowship provided through Clark University’s Global Scholars program. J.P.M. acknowledges a summer fellowship from PCI Synthesis Inc

Publication Title

Synlett

Publication Date

3-1-2023

Volume

34

Issue

4

First Page

388

Last Page

392

ISSN

0936-5214

DOI

10.1055/s-0042-1751397

Keywords

cyclization, glutamyl hydrazides, hydrazides, inhibitors, peptides, unnatural amino acids

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