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This waste is generally discarded. In this study, skin was used as a source of proteins that were hydrolysed using Trypsin, Esperase\u00ae or Alcalase\u00ae, which released peptides with antioxidant potential and, in particular, antihypertensive (ACE inhibition), hypoglycemic (DPP-IV inhibition) and\/or nootropic (PEP inhibition) potential. Among the three enzymes tested, Esperase\u00ae and Alcalase produced hydrolysates with potent ACE-, DPP-IV- and PEP-inhibiting properties. These hydrolysates underwent chromatography fractionation, and the composition of the most bioactive fractions was analysed using HPLC-MS-MS. The fractions with the highest bioactivity exhibited very low IC50 values (16 and 66 \u00b5g\/mL for ACE inhibition, 97 \u00b5g\/mL for DPP-IV inhibition and 55 \u00b5g\/mL for PEP inhibition) and were mainly derived from the hydrolysate obtained using Esperase\u00ae. The presence of Leu at the C-terminal appeared to be crucial for the ACE inhibitory activity of these fractions. The DPP-IV inhibitory activity of peptides seemed to be determined by the presence of Pro or Ala in the second position from the N-terminus, and Gly and\/or Pro in the last C-terminal positions. Similarly, the presence of Pro in the peptides present in the best PEP inhibitory fraction seemed to be important in the inhibitory effect. These results demonstrate that the skin of the Argentine shortfin squid is a valuable source of bioactive peptides, suitable for incorporation into human nutrition as nutraceuticals and food supplements.<\/jats:p>","DOI":"10.3390\/md22040156","type":"journal-article","created":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T12:09:40Z","timestamp":1711627780000},"page":"156","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Protein Hydrolysis as a Way to Valorise Squid-Processing Byproducts: Obtaining and Identification of ACE, DPP-IV and PEP Inhibitory Peptides"],"prefix":"10.3390","volume":"22","author":[{"given":"Hajer","family":"Bougatef","sequence":"first","affiliation":[{"name":"Laboratory for the Improvement of Plants and Valorization of Agroresources, National School of Engineering of Sfax (ENIS), University of Sfax, Sfax 3038, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Assaad","family":"Sila","sequence":"additional","affiliation":[{"name":"Laboratory for the Improvement of Plants and Valorization of Agroresources, National School of Engineering of Sfax (ENIS), University of Sfax, Sfax 3038, Tunisia"},{"name":"Department of Life Sciences, Faculty of Sciences of Gafsa, University of Gafsa, Gafsa 2100, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6670-8368","authenticated-orcid":false,"given":"Ali","family":"Bougatef","sequence":"additional","affiliation":[{"name":"Laboratory for the Improvement of Plants and Valorization of Agroresources, National School of Engineering of Sfax (ENIS), University of Sfax, Sfax 3038, Tunisia"},{"name":"High Institute of Biotechnology of Sfax, University of Sfax, Sfax 3038, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9643-1619","authenticated-orcid":false,"given":"Oscar","family":"Mart\u00ednez-Alvarez","sequence":"additional","affiliation":[{"name":"Institute of Food Science, Technology and Nutrition (ICTAN, CSIC), 6 Jos\u00e9 Antonio Novais St, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1590\/fst.24719","article-title":"Structural and Biological Properties of Protein Hydrolysates from Seafood By-Products: A Review Focused on Fishery Effluents","volume":"40","year":"2020","journal-title":"Food Sci. 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