Deciphering the self-assembly mechanisms of three diphenylalanine derivatives using infrared probe technique and scanning electron microscopy

Yao Wang; Ziqi Wang; Lujuan Yang; Ziyang Liu; Chunfang Zhang; Yanli Shang; Gang Ma

doi:10.1016/j.saa.2024.125522

Deciphering the self-assembly mechanisms of three diphenylalanine derivatives using infrared probe technique and scanning electron microscopy

Spectrochim Acta A Mol Biomol Spectrosc. 2024 Dec 3:329:125522. doi: 10.1016/j.saa.2024.125522. Online ahead of print.

Authors

Yao Wang¹, Ziqi Wang¹, Lujuan Yang¹, Ziyang Liu¹, Chunfang Zhang², Yanli Shang³, Gang Ma⁴

Affiliations

¹ Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Key Laboratory of Analytical Science and Technology of Hebei Province, State Key Laboratory of New Pharmaceutical Preparations and Excipients, Hebei Research Center of the Basic Discipline of Synthetic Chemistry, College of Chemistry and Materials Science, Hebei University, Baoding 071002, China.
² Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Key Laboratory of Analytical Science and Technology of Hebei Province, State Key Laboratory of New Pharmaceutical Preparations and Excipients, Hebei Research Center of the Basic Discipline of Synthetic Chemistry, College of Chemistry and Materials Science, Hebei University, Baoding 071002, China. Electronic address: zhangcf@hbu.edu.cn.
³ Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Key Laboratory of Analytical Science and Technology of Hebei Province, State Key Laboratory of New Pharmaceutical Preparations and Excipients, Hebei Research Center of the Basic Discipline of Synthetic Chemistry, College of Chemistry and Materials Science, Hebei University, Baoding 071002, China. Electronic address: ylshang@hbu.edu.cn.
⁴ Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Key Laboratory of Analytical Science and Technology of Hebei Province, State Key Laboratory of New Pharmaceutical Preparations and Excipients, Hebei Research Center of the Basic Discipline of Synthetic Chemistry, College of Chemistry and Materials Science, Hebei University, Baoding 071002, China. Electronic address: gangma@hbu.edu.cn.

PMID: 39662193
DOI: 10.1016/j.saa.2024.125522

Abstract

Understanding the nucleation mechanism of peptide self-assembly is fundamental for the design and application of peptide-based materials. To this end, we herein explored the self-assembly processes of three diphenylalanine (FF) derivatives, Boc-XF, Boc-FX, and Boc-FF, where X is p-cyanophenylalanine with the cyano group being an infrared (IR) probe. Using IR probe technique and scanning electron microscopy (SEM), we revealed that the self-assembly of Boc-XF followed a three-step non-classical nucleation mechanism. Such a complex mechanism involved the presence of metastable spherical and fibrillar intermediates towards the final mature fibril phase. We further compared the self-assembly mechanism of Boc-XF with that of Boc-FF and Boc-FX and explored the potential impact of side-chain mutation on the peptide self-assembly mechanism. Our research provided a nice example of how to use a combined approach of IR probe technique and SEM to reveal the complex nucleation mechanism of peptide self-assembly.

Keywords: Diphenylalanine; FTIR spectroscopy; Infrared probe; Nucleation; Self-assembly.