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© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

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 (∆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-ΔPhe were obtained as a pair (D,L,Z)/(L,L,Z) of diastereomers. Their scrambled sequence analogues Phe-Hph-ΔPhe were obtained also as a diastereomeric (L,D,Z)/(L,L,Z) pair. The effect of stereochemistry (homo- vs. hetero-chirality) and sequence (Phe-∆Phe vs. Hph-∆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.

Details

Title
Tripeptides Featuring Dehydrophenylalanine and Homophenylalanine: Homo- Versus Hetero-Chirality and Sequence Effects on Self-Assembly and Gelation
Author
Carvalho, André F 1   VIAFID ORCID Logo  ; Pereira, Teresa 1   VIAFID ORCID Logo  ; Oliveira, Carlos 1   VIAFID ORCID Logo  ; Figueiredo, Pedro 2   VIAFID ORCID Logo  ; Carvalho, Alexandra 3 ; Pereira, David M 4   VIAFID ORCID Logo  ; Hilliou, Loic 5   VIAFID ORCID Logo  ; Bañobre-López, Manuel 6   VIAFID ORCID Logo  ; Xu, Bing 7   VIAFID ORCID Logo  ; Ferreira, Paula M T 1   VIAFID ORCID Logo  ; Martins, José A 1   VIAFID ORCID Logo 

 Center of Chemistry, University of Minho, 4710-057 Braga, Portugal[email protected] (C.O.) 
 CNC—Center for Neuroscience and Cell Biology, Institute for Interdisciplinary Research (IIIUC), University of Coimbra, 3004-504 Coimbra, Portugal; PhD Programme in Experimental Biology and Biomedicine, Institute for Interdisciplinary Research (IIIUC), University of Coimbra, Casa Costa Alemão, 3030-789 Coimbra, Portugal 
 CNC—Center for Neuroscience and Cell Biology, Institute for Interdisciplinary Research (IIIUC), University of Coimbra, 3004-504 Coimbra, Portugal; Almac Sciences, Department of Biocatalysis and Isotope Chemistry, Almac House, 20 Seagoe Industrial Estate, Craigavon BT63 5QD, UK 
 REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, R. Jorge Viterbo Ferreira, n 228, 4050-313 Porto, Portugal 
 Institute for Polymers and Composites, University of Minho, 4800-058 Guimarães, Portugal; [email protected] 
 International Iberian Nanotechnology Laboratory (INL), Av. Mestre José Veiga s/n, 4715-330 Braga, Portugal; [email protected] 
 Department of Chemistry, Brandeis University, 415 South Street, Waltham, MA 02453, USA 
First page
164
Publication year
2025
Publication date
2025
Publisher
MDPI AG
e-ISSN
23102861
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3181476521
Copyright
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.