Heterocyclic Scaffolds in the Design of Peptidomimetic Integrin Ligands: Synthetic Strategies, Structural Aspects, and Biological Activity

Author(s): Rossella De Marco, Giacomo Mazzotti, Arianna Greco, Luca Gentilucci

Journal Name: Current Topics in Medicinal Chemistry

Volume 16 , Issue 3 , 2016

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Graphical Abstract:


The integrin receptors represent valuable targets for therapeutic interventions; being overexpressed in many pathological states, their inhibition can be effective to treat a number of severe diseases. Since integrin functions are mediated by interactions with ECM protein ligands, the inhibition can be achieved by interfering with such interactions using small mimetics of the integrin-ligand recognition motifs (e.g. RGD, LDV, etc.). In this review, we focus on the antagonists with peptideheterocycle hybrid structures. The introduction of well-designed scaffolds has met considerable success in the rational design of highly stable, bioavailable, and conformationally defined antagonists. Two main approaches are discussed herein. The first approach is the use of scaffolds external to the main recognition motifs, aimed at improving conformational definition. In the second approach, heterocyclic cores are introduced within the recognition motifs, giving access to libraries of 3D diverse candidate antagonists.

Keywords: Antagonist, Cancer, Conformational analysis, Dipeptide scaffold, Heterocycle, Molecular docking, Peptidomimetic.

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Article Details

Year: 2016
Published on: 07 October, 2015
Page: [343 - 359]
Pages: 17
DOI: 10.2174/1568026615666150812121614
Price: $65

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