{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T14:40:48Z","timestamp":1775486448086,"version":"3.50.1"},"reference-count":37,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T00:00:00Z","timestamp":1727654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding of CQUM","award":["UID\/QUI\/00686\/2019"],"award-info":[{"award-number":["UID\/QUI\/00686\/2019"]}]},{"name":"Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding of CQUM","award":["UIDP\/CTM\/05256\/2020"],"award-info":[{"award-number":["UIDP\/CTM\/05256\/2020"]}]},{"name":"Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding of CQUM","award":["UIDB\/05256\/2020"],"award-info":[{"award-number":["UIDB\/05256\/2020"]}]},{"name":"Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding of CQUM","award":["UIDB\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020"]}]},{"name":"IPC","award":["UID\/QUI\/00686\/2019"],"award-info":[{"award-number":["UID\/QUI\/00686\/2019"]}]},{"name":"IPC","award":["UIDP\/CTM\/05256\/2020"],"award-info":[{"award-number":["UIDP\/CTM\/05256\/2020"]}]},{"name":"IPC","award":["UIDB\/05256\/2020"],"award-info":[{"award-number":["UIDB\/05256\/2020"]}]},{"name":"IPC","award":["UIDB\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020"]}]},{"name":"REQUIMTE\/LAQV","award":["UID\/QUI\/00686\/2019"],"award-info":[{"award-number":["UID\/QUI\/00686\/2019"]}]},{"name":"REQUIMTE\/LAQV","award":["UIDP\/CTM\/05256\/2020"],"award-info":[{"award-number":["UIDP\/CTM\/05256\/2020"]}]},{"name":"REQUIMTE\/LAQV","award":["UIDB\/05256\/2020"],"award-info":[{"award-number":["UIDB\/05256\/2020"]}]},{"name":"REQUIMTE\/LAQV","award":["UIDB\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gels"],"abstract":"<jats:p>Self-assembly of peptide building blocks offers unique opportunities for bottom-up preparation of exquisite nanostructures, nanoarchitectures, and nanostructured bulk materials, namely hydrogels. In this work we describe the synthesis, characterization, gelation, and rheological properties of new dehydrotripeptides, Cbz-L-Lys(Cbz)-L,D-Asp-\u2206Phe-OH and (2-Naph)-L-Lys(2-Naph)-L,D-Asp-\u2206Phe-OH, containing a N-terminal lysine residue N\u03b1,\u03b5-bis-capped with carboxybenzyl (Cbz) and 2-Naphthylacetyl (2-Naph) aromatic moieties, an aspartic acid residue (Asp), and a C-terminal dehydrophenylalanine (\u2206Phe) residue. The dehydrotripeptides were obtained as diastereomeric mixtures (L,L,Z and L,D,Z), presumably via aspartimide chemistry. The dehydrotripeptides afforded hydrogels at exceedingly low concentrations (0.1 and 0.04 wt%). The hydrogels revealed exceptional elasticity (G\u2019 = 5.44 \u00d7 104 and 3.43 \u00d7 106 Pa) and self-healing properties. STEM studies showed that the diastereomers of the Cbz-capped peptide undergo co-assembly, generating a fibrillar 3D network, while the diastereomers of the 2-Naph-capped dehydropeptide seem to undergo self-sorting, originating a fibril network with embedded spheroidal nanostructures. The 2-Naph-capped hydrogel displayed full fast recovery following breakup by a mechanical stimulus. Spheroidal nanostructures are absent in the recovered hydrogel, as seen by STEM, suggesting that the mechanical stimulus triggers rearrangement of the spheroidal nanostructures into fibers. Overall, this study demonstrates that diastereomeric mixtures of peptides can be efficacious gelators. Importantly, these results suggest that the structure (size, aromaticity) of the capping group can have a directing effect on the self-assembly (co-assembly vs. self-sorting) of diastereomers. The cytotoxicity of the newly synthesized gelators was evaluated using human keratinocytes (HaCaT cell line). The results indicated that the two gelators exhibited some cytotoxicity, having a small impact on cell viability. In sustained release experiments, the influence of the charge on model drug compounds was assessed in relation to their release rate from the hydrogel matrix. The hydrogels demonstrated sustained release for methyl orange (anionic), while methylene blue (cationic) was retained within the network.<\/jats:p>","DOI":"10.3390\/gels10100629","type":"journal-article","created":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T07:19:37Z","timestamp":1727680777000},"page":"629","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["New Supramolecular Hydrogels Based on Diastereomeric Dehydrotripeptide Mixtures for Potential Drug Delivery Applications"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5340-4151","authenticated-orcid":false,"given":"Carlos B. P.","family":"Oliveira","sequence":"first","affiliation":[{"name":"Chemistry Centre, School of Sciences, University of Minho, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4816-6371","authenticated-orcid":false,"given":"Andr\u00e9","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Chemistry Centre, School of Sciences, University of Minho, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8500-7364","authenticated-orcid":false,"given":"Renato B.","family":"Pereira","sequence":"additional","affiliation":[{"name":"REQUIMTE\/LAQV, Laborat\u00f3rio de Farmacognosia, Departamento de Qu\u00edmica, Faculdade de Farm\u00e1cia, Universidade do Porto, R. Jorge Viterbo Ferreira, n228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0384-7592","authenticated-orcid":false,"given":"David M.","family":"Pereira","sequence":"additional","affiliation":[{"name":"REQUIMTE\/LAQV, Laborat\u00f3rio de Farmacognosia, Departamento de Qu\u00edmica, Faculdade de Farm\u00e1cia, Universidade do Porto, R. Jorge Viterbo Ferreira, n228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9936-8088","authenticated-orcid":false,"given":"Loic","family":"Hilliou","sequence":"additional","affiliation":[{"name":"Institute for Polymers and Composites, University of Minho, 4800-058 Guimar\u00e3es, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5550-4535","authenticated-orcid":false,"given":"Peter J.","family":"Jervis","sequence":"additional","affiliation":[{"name":"Chemistry Centre, School of Sciences, University of Minho, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9323-3978","authenticated-orcid":false,"given":"Jos\u00e9 A.","family":"Martins","sequence":"additional","affiliation":[{"name":"Chemistry Centre, School of Sciences, University of Minho, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3279-6731","authenticated-orcid":false,"given":"Paula M. T.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Chemistry Centre, School of Sciences, University of Minho, 4710-057 Braga, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1039\/C9BM01304K","article-title":"Short to ultrashort peptide-based hydrogels as a platform for biomedical applications","volume":"8","author":"Yadav","year":"2020","journal-title":"Biomater. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.eurpolymj.2017.12.004","article-title":"Recent advances in smart hydrogels for biomedical applications: From self-assembly to functional approaches","volume":"99","author":"Ferreira","year":"2018","journal-title":"Eur. Polym. 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