title: New potent αvβ3 integrin ligands based on azabicycloalkane (γ,α)-dipeptide mimics.
abstract: We have designed a new synthetic strategy for the preparation of a new class of cyclic RGD integrin ligands in which the azabicycloalkane scaffold can be envisaged as a (γ,α) dipeptide mimic. The synthesis and in vitro biological evaluation of these RGD derivatives, as well as the computational study of their conformational properties and binding modes to αVβ3 integrin are described. Compound has shown to be a promising candidate as αVβ3 integrin antagonist able to interfere with both cell adhesion and movement on vitronectin with no evidence of cytotoxic effects.
authors.affiliation: Centro Interdisciplinare Studi Biomolecolari e Applicazioni Industriali, Università degli Studi di Milano, Via Fantoli 16/15, I-20138, Milano.
authors.forename: M
authors.initials: M
authors.lastname: Pilkington-Miksa
authors.affiliation: Centro Interdisciplinare Studi Biomolecolari e Applicazioni Industriali, Università degli Studi di Milano, Via Fantoli 16/15, I-20138, Milano.
authors.forename: E M V
authors.initials: EM
authors.lastname: Araldi
authors.affiliation: Istituto di Scienze e Tecnologie Molecolari, Consiglio Nazionale delle Ricerche, Via C. Golgi 19, I-20133, Milano. Leonardo.manzoni@istm.cnr.it.
authors.forename: D
authors.initials: D
authors.lastname: Arosio
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi 19, I-20133, Milano.
authors.forename: L
authors.initials: L
authors.lastname: Belvisi
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi 19, I-20133, Milano.
authors.forename: M
authors.initials: M
authors.lastname: Civera
authors.affiliation: Istituto di Scienze e Tecnologie Molecolari, Consiglio Nazionale delle Ricerche, Via C. Golgi 19, I-20133, Milano. Leonardo.manzoni@istm.cnr.it.
authors.forename: L
authors.initials: L
authors.lastname: Manzoni
mesh_terms: D000473:Alkanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D053961:Azabicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
chemical_list: D000473:Alkanes; D053961:Azabicyclo Compounds; D004151:Dipeptides; D039302:Integrin alphaVbeta3; D008024:Ligands