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The synthesis of this novel class of ligands was obtained by conjugation of linkers to the heterocyclic core via Huisgen-click reaction, with the aim to use them as \u201cshuttles\u201d for selective delivery of diagnostic agents to cancer cells, exploring the effects of the side chains in the interaction with the target. Compounds <jats:bold>17b<\/jats:bold> and <jats:bold>24<\/jats:bold> showed excellent potency towards \u03b1<jats:sub>5<\/jats:sub>\u03b2<jats:sub>1<\/jats:sub> integrin acting as selective antagonist and agonist respectively. Further investigations confirmed their effects on target receptor through the analysis of fibronectin-induced ERK1\/2 phosphorylation. In addition, confocal microscopy analysis allowed us to follow the fate of EGFP conjugated \u03b1<jats:sub>5<\/jats:sub>\u03b2<jats:sub>1<\/jats:sub> integrin and <jats:bold>17b<\/jats:bold> FITC-conjugated (compound <jats:bold>31<\/jats:bold>) inside the cells. Moreover, the stability in water solution at different values of pH and in bovine serum confirmed the possible exploitation of these peptidomimetic molecules for pharmaceutical application.<\/jats:p>","DOI":"10.1038\/s41598-020-64396-4","type":"journal-article","created":{"date-parts":[[2020,5,4]],"date-time":"2020-05-04T10:05:01Z","timestamp":1588586701000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Side chain effect in the modulation of \u03b1v\u03b23\/\u03b15\u03b21 integrin activity via clickable isoxazoline-RGD-mimetics: development of molecular delivery systems"],"prefix":"10.1038","volume":"10","author":[{"given":"Lucia","family":"Ferrazzano","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dario","family":"Corbisiero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleonora","family":"Potenza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Baiula","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha Deianira","family":"Dattoli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Santi","family":"Spampinato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Belvisi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Civera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Tolomelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,5,4]]},"reference":[{"key":"64396_CR1","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.jconrel.2011.09.063","volume":"161","author":"T Lammers","year":"2012","unstructured":"Lammers, T., Kiessling, F., Hennink, W. 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