Issue 11, 2023

Factors influencing the catalytic activity of metal-dependent histidine-rich peptides: sequence, conformation, stereochemistry, self-assembly or their interplay?

Abstract

The sequence-to-function relationship of peptide-based catalysts remains a challenge, as even subtle modifications at the sequence level can alternate their catalytic activity. A set of linear and cyclic histidine-rich peptides was synthesized to assess the impact of amino acid disposition, cyclization, and incorporation of D-amino acids on their ability to self-assemble, coordinate Zn2+ ions, and show intrinsic hydrolase-like activity. Self-assembly into β-sheets was confirmed for both linear peptides and one cyclic analogue (cy-hh) by FTIR, ThT binding, CD, and AFM. Interestingly, only peptide A demonstrated efficient ester hydrolysis of p-NPA, p-NPB and p-NPO substrates, indicative of its effective Zn2+ coordination. Our findings highlight that increased rigidity of the peptide can hinder metal ion coordination by limiting the necessary conformational adjustments for optimal Zn2+ binding. These insights into the structural changes underlying the function of short peptides offer valuable knowledge for the design of metal-dependent peptide-based catalysts.

Graphical abstract: Factors influencing the catalytic activity of metal-dependent histidine-rich peptides: sequence, conformation, stereochemistry, self-assembly or their interplay?

Supplementary files

Article information

Article type
Paper
Submitted
18 Jul 2023
Accepted
13 Sep 2023
First published
13 Sep 2023
This article is Open Access
Creative Commons BY license

Mol. Syst. Des. Eng., 2023,8, 1371-1380

Factors influencing the catalytic activity of metal-dependent histidine-rich peptides: sequence, conformation, stereochemistry, self-assembly or their interplay?

P. Janković, M. Babić, M. Perčić, A. S. Pina and D. Kalafatovic, Mol. Syst. Des. Eng., 2023, 8, 1371 DOI: 10.1039/D3ME00117B

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