{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T13:41:08Z","timestamp":1765546868252,"version":"build-2065373602"},"reference-count":25,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2021,12,3]],"date-time":"2021-12-03T00:00:00Z","timestamp":1638489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["UID\/Multi\/04349\/2020","UIDB\/00100\/2020","PTDC\/QUI-QIN\/0146\/2020","PTDC\/QUI-NUC\/30147\/2017","DFA\/BD\/4978\/2020","SFRH\/BD\/135915\/2018","CEECIND\/00630\/2017"],"award-info":[{"award-number":["UID\/Multi\/04349\/2020","UIDB\/00100\/2020","PTDC\/QUI-QIN\/0146\/2020","PTDC\/QUI-NUC\/30147\/2017","DFA\/BD\/4978\/2020","SFRH\/BD\/135915\/2018","CEECIND\/00630\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Considering our interest in the use of peptides as potential target-specific drugs or as delivery vectors of metallodrugs for various biomedical applications, it is crucial to explore improved synthetic methodologies to accomplish the highest peptide crude purity in the shortest time possible. Therefore, we compared \u201cclassical\u201d fluorenylmethoxycarbonyl (Fmoc)-solid phase peptide synthesis (SPPS) with ultrasound(US)-assisted SPPS based on the preparation of three peptides, namely the fibroblast growth factor receptor 3(FGFR3)-specific peptide Pep1 (VSPPLTLGQLLS-NH2) and the novel peptides Pep2 (RQMATADEA-NH2) and Pep3 (AAVALLPAVLLALLAPRQMATADEA-NH2), which are being developed aimed at interfering with the intracellular protein-protein interaction(PPI) RANK-TRAF6. Our results demonstrated that US-assisted SPPS led to a 14-fold (Pep1) and 4-fold time reduction (Pep2) in peptide assembly compared to the \u201cclassical\u201d method. Interestingly, US-assisted SPPS yielded Pep1 in higher purity (82%) than the \u201cclassical\u201d SPPS (73%). The significant time reduction combined with high crude peptide purity attained prompted use to apply US-assisted SPPS to the large peptide Pep3, which displays a high number of hydrophobic amino acids and homooligo-sequences. Remarkably, the synthesis of this 25-mer peptide was attained during a \u201cworking day\u201d (347 min) in moderate purity (approx. 49%). In conclusion, we have reinforced the importance of using US-SPPS towards facilitating the production of peptides in shorter time with increased efficacy in moderate to high crude purity. This is of special importance for long peptides such as the case of Pep3.<\/jats:p>","DOI":"10.3390\/molecules26237349","type":"journal-article","created":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T03:10:38Z","timestamp":1638760238000},"page":"7349","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Ultrasonication Improves Solid Phase Synthesis of Peptides Specific for Fibroblast Growth Factor Receptor and for the Protein-Protein Interface RANK-TRAF6"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3665-9571","authenticated-orcid":false,"given":"R\u00faben D. M.","family":"Silva","sequence":"first","affiliation":[{"name":"Centro de Ci\u00eancias e Tecnologias Nucleares, Instituto Superior T\u00e9cnico, Universidade de Lisboa, CTN, Estrada Nacional 10 (km 139.7), Bobadela, 2695-066 Loures, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3741-2386","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Franco Machado","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias e Tecnologias Nucleares, Instituto Superior T\u00e9cnico, Universidade de Lisboa, CTN, Estrada Nacional 10 (km 139.7), Bobadela, 2695-066 Loures, Portugal"},{"name":"Centro de Qu\u00edmica Estrutural and Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5160-1357","authenticated-orcid":false,"given":"Kyle","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias e Tecnologias Nucleares, Instituto Superior T\u00e9cnico, Universidade de Lisboa, CTN, Estrada Nacional 10 (km 139.7), Bobadela, 2695-066 Loures, Portugal"}]},{"given":"Francisco M.","family":"Lucas","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias e Tecnologias Nucleares, Instituto Superior T\u00e9cnico, Universidade de Lisboa, CTN, Estrada Nacional 10 (km 139.7), Bobadela, 2695-066 Loures, Portugal"}]},{"given":"Salete","family":"Batista","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias e Tecnologias Nucleares, Instituto Superior T\u00e9cnico, Universidade de Lisboa, CTN, Estrada Nacional 10 (km 139.7), Bobadela, 2695-066 Loures, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1056-1007","authenticated-orcid":false,"given":"Rita","family":"Melo","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias e Tecnologias Nucleares, Instituto Superior T\u00e9cnico, Universidade de Lisboa, CTN, Estrada Nacional 10 (km 139.7), Bobadela, 2695-066 Loures, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0233-8243","authenticated-orcid":false,"given":"T\u00e2nia S.","family":"Morais","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural and Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7847-4906","authenticated-orcid":false,"given":"Jo\u00e3o D. G.","family":"Correia","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias e Tecnologias Nucleares, Instituto Superior T\u00e9cnico, Universidade de Lisboa, CTN, Estrada Nacional 10 (km 139.7), Bobadela, 2695-066 Loures, Portugal"},{"name":"Departamento de Engenharia e Ci\u00eancias Nucleares, Instituto Superior T\u00e9cnico, Universidade de Lisboa, CTN, Estrada Nacional 10 (km 139.7), Bobadela, 2695-066 Loures, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1002\/ejic.201601094","article-title":"Functionalization of Ruthenium(II) Terpyridine Complexes with Cyclic RGD Peptides to Target Integrin Receptors in Cancer Cells","volume":"12","author":"Hahn","year":"2017","journal-title":"Eur. J. Inorg. 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