Tripeptides Featuring Dehydrophenylalanine and Homophenylalanine: Homo- Versus Hetero-Chirality and Sequence Effects on Self-Assembly and Gelation

• Type: Article in International Scientific Journal
• Date: 2025

Authors

Carvalho, AF (Author) Other; Pereira, T (Author) Other; Oliveira, C (Author) Other; Figueiredo, P (Author) Other; Carvalho, A (Author) Other; David M Pereira (Author) FFUP; L. Hilliou (Author) Other; Bañobre-López, M (Author) Other; Xu, B (Author) Other; Ferreira, PMT (Author) Other; Martins, JA (Author) Other

Journal

Title: GELS

Vol. 11

Final page: 164

Indexing

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Other information

Authenticus ID: P-018-4TK

DOI: 10.3390/gels11030164

Abstract (EN): Over the years, our research group developed dehydrodipeptides N-capped with aromatic moieties as protease-resistant efficacious hydrogelators, affording self-assembled hydrogels at low (critical) concentrations. Dehydrotripeptides, with different dipeptide sequences and (D,L) stereochemistry, open a wider chemical space for the development of self-assembled soft nanomaterials. In this work, a small library of N-succinylated dehydrotripeptides containing a C-terminal dehydrophenylalanine (triangle Phe) residue and a scrambled dipeptide sequence with phenylalanine (Phe) and homophenylalanine (Hph) (L-Phe-L,D-Hph and L,D-Hph-L-Phe) was synthesized and characterized as a potential hydrogelator. Two pairs of diastereomeric tripeptides were synthesized, both as C-protected methyl esters and as deprotected dicarboxylic acids. Peptides with the sequence Hph-Phe-Delta Phe were obtained as a pair (D,L,Z)/(L,L,Z) of diastereomers. Their scrambled sequence analogues Phe-Hph-Delta Phe were obtained also as a diastereomeric (L,D,Z)/(L,L,Z) pair. The effect of stereochemistry (homo- vs. hetero-chirality) and sequence (Phe-triangle Phe vs. Hph-triangle Phe motif) on the self-assembly, biocompatibility, gelation and rheological properties of the hydrogels was studied in this work. Accessible, both as C-protected methyl esters and as dicarboxylic acids, N-succinylated dehydrotripeptides are interesting molecular architectures for the development of supramolecular nanomaterials. Interestingly, our results do not comply with the well-documented proposition that heterochiral peptides display much higher self-assembly propensity and gelation ability than their homochiral counterparts. Further studies will be necessary to fully understand the interplay between peptide sequence and homo- and hetero-chirality on peptide self-assembly and on the properties of their supramolecular materials.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 23