{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T15:09:19Z","timestamp":1769180959238,"version":"3.49.0"},"reference-count":60,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,5,11]],"date-time":"2021-05-11T00:00:00Z","timestamp":1620691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wroclaw Research Center EIT+ under the project \u201cBiotechnologies and advanced medical technologies \u2013 BioMed\u201d","award":["POIG 01.01.02-02-003\/08-00"],"award-info":[{"award-number":["POIG 01.01.02-02-003\/08-00"]}]},{"name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades (MCIU), Agencia Estatal de Investigaci\u00f3n (AEI) y Fondo Europeo de Desarrollo Regional (FEDER)","award":["RTI2018-101818-B-I00, UE"],"award-info":[{"award-number":["RTI2018-101818-B-I00, UE"]}]},{"name":"Gobierno Vasco (GV)","award":["IT 992-16"],"award-info":[{"award-number":["IT 992-16"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Phosphinate pseudopeptide are analogs of peptides containing phosphinate moiety in a place of the amide bond. Due to this, the organophosphorus fragment resembles the tetrahedral transition state of the amide bond hydrolysis. Additionally, it is also capable of coordinating metal ions, for example, zinc or magnesium ions. These two properties of phosphinate pseudopeptides make them an ideal candidate for metal-related protease inhibitors. This research investigates the influence of additional residue in the P2 position on the inhibitory properties of phosphinopeptides. The synthetic strategy is proposed, based on retrosynthetic analysis. The N-C-P bond formation in the desired compounds is conveniently available from the three-component condensation of appropriate amino components, aldehydes, and hypophosphorous acid. One of the crucial synthetic steps is the careful selection of the protecting groups for all the functionals. Determination of the inhibitor activity of the obtained compounds has been done using UV-Vis spectroscopy and standard substrate L-Leu-p-nitroanilide toward the enzymes isolated from the porcine kidney (SsLAP, Sus scrofa Leucine aminopeptidase) and barley seeds (HvLAP, Hordeum vulgare Leucine aminopeptidase). An efficient procedure for the preparation of phosphinotripeptides has been performed. Activity test shown that introduction of additional residue into P2 position obtains the micromolar range inhibitors of SsLAP and HvLAP. Moreover, careful selection of the residue in the P2 position should improve its selectivity toward mammalian and plant leucyl aminopeptidases.<\/jats:p>","DOI":"10.3390\/ijms22105090","type":"journal-article","created":{"date-parts":[[2021,5,11]],"date-time":"2021-05-11T22:53:40Z","timestamp":1620773620000},"page":"5090","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Phosphinotripeptidic Inhibitors of Leucylaminopeptidases"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4931-5452","authenticated-orcid":false,"given":"Micha\u0142","family":"Jewgi\u0144ski","sequence":"first","affiliation":[{"name":"Department of Bioorganic Chemistry, Wroc\u0142aw University of Science and Technology, Wybrze\u017ce Wyspia\u0144skiego 27, 50-370 Wroc\u0142aw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kinga","family":"Haremza","sequence":"additional","affiliation":[{"name":"Department of Bioorganic Chemistry, Wroc\u0142aw University of Science and Technology, Wybrze\u017ce Wyspia\u0144skiego 27, 50-370 Wroc\u0142aw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1315-4263","authenticated-orcid":false,"given":"Jes\u00fas M.","family":"de los Santos","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry I, Faculty of Pharmacy, Lascaray Research Center, University of the Basque Country (UPV\/EHU), Paseo de la Universidad, 7, 01006 Vitoria, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zouhair","family":"Es Sbai","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry I, Faculty of Pharmacy, Lascaray Research Center, University of the Basque Country (UPV\/EHU), Paseo de la Universidad, 7, 01006 Vitoria, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bartosz","family":"Oszywa","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, University of Opole, Oleska 48, 45-052 Opole, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3382-9697","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Pawe\u0142czak","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, University of Opole, Oleska 48, 45-052 Opole, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6365-0324","authenticated-orcid":false,"given":"Francisco","family":"Palacios","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry I, Faculty of Pharmacy, Lascaray Research Center, University of the Basque Country (UPV\/EHU), Paseo de la Universidad, 7, 01006 Vitoria, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2943-2838","authenticated-orcid":false,"given":"Rafa\u0142","family":"Latajka","sequence":"additional","affiliation":[{"name":"Department of Bioorganic Chemistry, Wroc\u0142aw University of Science and Technology, Wybrze\u017ce Wyspia\u0144skiego 27, 50-370 Wroc\u0142aw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.2174\/1385272043370177","article-title":"Phosphinic Peptides: Synthetic Approaches and Biochemical Evaluation as Zn-Metalloprotease Inhibitors","volume":"8","author":"Yiotakis","year":"2004","journal-title":"Curr. 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