{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T08:03:44Z","timestamp":1768464224632,"version":"3.49.0"},"reference-count":57,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T00:00:00Z","timestamp":1685491200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education, University and Research","award":["2020833Y75"],"award-info":[{"award-number":["2020833Y75"]}]},{"name":"Ministry of Education, University and Research","award":["232 1 December 2016"],"award-info":[{"award-number":["232 1 December 2016"]}]},{"name":"Ministry of Education, University and Research","award":["#18668"],"award-info":[{"award-number":["#18668"]}]},{"name":"Department of Excellence Program","award":["2020833Y75"],"award-info":[{"award-number":["2020833Y75"]}]},{"name":"Department of Excellence Program","award":["232 1 December 2016"],"award-info":[{"award-number":["232 1 December 2016"]}]},{"name":"Department of Excellence Program","award":["#18668"],"award-info":[{"award-number":["#18668"]}]},{"name":"Fondazione CarisBo","award":["2020833Y75"],"award-info":[{"award-number":["2020833Y75"]}]},{"name":"Fondazione CarisBo","award":["232 1 December 2016"],"award-info":[{"award-number":["232 1 December 2016"]}]},{"name":"Fondazione CarisBo","award":["#18668"],"award-info":[{"award-number":["#18668"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Integrin receptors mediate cell\u2013cell interactions via the recognition of cell-adhesion glycoproteins, as well as via the interactions of cells with proteins of the extracellular matrix, and upon activation they transduce signals bi-directionally across the cell membrane. In the case of injury, infection, or inflammation, integrins of \u03b22 and \u03b14 families participate in the recruitment of leukocytes, a multi-step process initiated by the capturing of rolling leukocytes and terminated by their extravasation. In particular, \u03b14\u03b21 integrin is deeply involved in leukocyte firm adhesion preceding extravasation. Besides its well-known role in inflammatory diseases, \u03b14\u03b21 integrin is also involved in cancer, being expressed in various tumors and showing an important role in cancer formation and spreading. Hence, targeting this integrin represents an opportunity for the treatment of inflammatory disorders, some autoimmune diseases, and cancer. In this context, taking inspiration from the recognition motives of \u03b14\u03b21 integrin with its natural ligands FN and VCAM-1, we designed minimalist \u03b1\/\u03b2 hybrid peptide ligands, with our approach being associated with a retro strategy. These modifications are expected to improve the compounds\u2019 stability and bioavailability. As it turned out, some of the ligands were found to be antagonists, being able to inhibit the adhesion of integrin-expressing cells to plates coated with the natural ligands without inducing any conformational switch and any activation of intracellular signaling pathways. An original model structure of the receptor was generated using protein\u2013protein docking to evaluate the bioactive conformations of the antagonists via molecular docking. Since the experimental structure of \u03b14\u03b21 integrin is still unknown, the simulations might also shed light on the interactions between the receptor and its native protein ligands.<\/jats:p>","DOI":"10.3390\/ijms24119588","type":"journal-article","created":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T03:06:00Z","timestamp":1685588760000},"page":"9588","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Design, Pharmacological Characterization, and Molecular Docking of Minimalist Peptidomimetic Antagonists of \u03b14\u03b21 Integrin"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0363-0633","authenticated-orcid":false,"given":"Monica","family":"Baiula","sequence":"first","affiliation":[{"name":"Department of Pharmacy and Biotechnology, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Anselmi","sequence":"additional","affiliation":[{"name":"Department of Chemistry \u201cG. Ciamician\u201d, University of Bologna, Via Selmi 2, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0200-1712","authenticated-orcid":false,"given":"Francesco","family":"Musiani","sequence":"additional","affiliation":[{"name":"Laboratory of Bioinorganic Chemistry, Department of Pharmacy and Biotechnology, University of Bologna, Viale Fanin 40, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1063-7067","authenticated-orcid":false,"given":"Alessia","family":"Ghidini","sequence":"additional","affiliation":[{"name":"Department of Chemistry \u201cG. Ciamician\u201d, University of Bologna, Via Selmi 2, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8743-7859","authenticated-orcid":false,"given":"Jacopo","family":"Carbone","sequence":"additional","affiliation":[{"name":"Department of Chemistry \u201cG. Ciamician\u201d, University of Bologna, Via Selmi 2, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1836-6882","authenticated-orcid":false,"given":"Alberto","family":"Caligiana","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02912, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Maurizio","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Biotechnology, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Santi","family":"Spampinato","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Biotechnology, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9134-3161","authenticated-orcid":false,"given":"Luca","family":"Gentilucci","sequence":"additional","affiliation":[{"name":"Department of Chemistry \u201cG. Ciamician\u201d, University of Bologna, Via Selmi 2, 40126 Bologna, Italy"},{"name":"Health Sciences & Technologies (HST) CIRI, University of Bologna, 40064 Ozzano Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"183206","DOI":"10.1016\/j.bbamem.2020.183206","article-title":"Chapter 22: Structural and signaling functions of integrins","volume":"1862","author":"Kadry","year":"2020","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/978-1-4419-6066-5_5","article-title":"Integrins and signal transduction","volume":"674","author":"Cabodi","year":"2010","journal-title":"Adv. Exp. Med. 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