{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T20:06:19Z","timestamp":1778097979089,"version":"3.51.4"},"reference-count":27,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T00:00:00Z","timestamp":1739491200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT, Portugal)","award":["UID\/QUI\/686\/2020"],"award-info":[{"award-number":["UID\/QUI\/686\/2020"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT, Portugal)","award":["2023.01012BD"],"award-info":[{"award-number":["2023.01012BD"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Small peptides with aromatic nuclei at the N-terminus have been shown to form bioactive, biocompatible, and biodegradable supramolecular peptide hydrogels. Novel heterocycle\u2013dipeptide conjugates with potential biological activity or application as drug carriers were synthesized by using S-(benzo[b]thiophene) and N,S-(thieno [2,3-b]pyridine and thieno[2,3-b]quinoline) heterocycles as N-protective groups for dipeptides l-Phe-l-Phe and l-Phe-l-Leu. The synthesis involved coupling heterocyclic carboxylic acids with trifluoroacetate salts of ethyl l-phenylalanyl-l-phenylalaninate and ethyl l-phenylalanyl- l-leucinate using HBTU and Et3N, producing the corresponding six N-heterocycle\u2013dipeptide ester conjugates, which were then hydrolyzed to the carboxylic acids. These conjugates were subjected to gelation tests in water starting from 0.4 wt% concentration of the conjugates, using a pH-lowering method with GdL. Among them, only the conjugate of benzo[b]thiophene with l-Phe-l-Phe-OH formed a hydrogel, with a gelation critical concentration of 0.15 wt% (GdL 0.6%) and a final pH of 6.8, which is important for biological applications. The hydrogel was characterized by STEM, revealing nanofibers with an average thickness of 17 nm that assemble into a 3D network capable of trapping water. Further rheological analysis demonstrated its viscoelastic behavior (G\u2032 = 3.03 \u00d7 103 Pa; G\u2033 = 3.28 \u00d7 102 Pa), comparable to the extracellular matrix of certain human tissues, crucial for biomedical applications.<\/jats:p>","DOI":"10.3390\/molecules30040869","type":"journal-article","created":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T03:20:52Z","timestamp":1739503252000},"page":"869","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Synthesis of S- and N,S-Heterocycle\u2013Dipeptide Conjugates for Supramolecular Hydrogel Formation"],"prefix":"10.3390","volume":"30","author":[{"given":"Ana-Morgana G. P.","family":"Silva","sequence":"first","affiliation":[{"name":"Centro de Qu\u00edmica, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1665-4343","authenticated-orcid":false,"given":"Maria F.","family":"Martins","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5340-4151","authenticated-orcid":false,"given":"Carlos B. P.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica, Universidade do Minho, Campus de Gualtar, 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":"Centro de Qu\u00edmica, Universidade do Minho, Campus de Gualtar, 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":"Centro de Qu\u00edmica, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4322-8035","authenticated-orcid":false,"given":"Maria-Jo\u00e3o R. P.","family":"Queiroz","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Vigata, M., Meinert, C., Hutmacher, D.W., and Bock, N. (2020). Hydrogels as Drug Delivery Systems: A Review of Current Characterization and Evaluation Techniques. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12121188"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"14976","DOI":"10.1039\/D0NR03785K","article-title":"Nanocomposite Hydrogels for Tissue Engineering Applications","volume":"12","author":"Zhao","year":"2020","journal-title":"Nanoscale"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Wiraja, C., Ning, X., Cui, M., and Xu, C. (2020). Hydrogel-Based Technologies for the Diagnosis of Skin Pathology. 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