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 7 2023
Accepted
13 9 2023
First published
13 9 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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