Role of Side-Chain Bioisosteres in Determining the Binding Affinity of Click Chemistry Derived RGD Peptidomimetics to αvβ3Integrin

Autor:	Pierangelo Fabbrizzi, S. Raspanti, Andrea Trabocchi, Gloria Menchi, Antonio Guarna
Rok vydání:	2014
Předmět:	chemistry.chemical_compound chemistry Peptidomimetic Organic Chemistry Aspartic acid Click chemistry Moiety Bioisostere Azide Physical and Theoretical Chemistry Guanidine Combinatorial chemistry Integrin binding
Zdroj:	European Journal of Organic Chemistry. 2014:7595-7604
ISSN:	1434-193X
Popis:	Triazole-containing Arg-Gly-Asp (RGD) peptidomimetics capable of interacting with αvβ3 integrin were developed through click chemistry. The role of the diverse range of guanidine bioisosteres for the arginine mimetic moiety was evaluated in vitro together with different appendages on the aspartic acid side of the peptidomimetic. The corresponding azides and alkynes were constructed through the application of simple modular reactions. Integrin binding assays allowed the best guanidine bioisostere for binding activity to be selected; the aromatic ring at the azide fragment bearing the aspartic acid moiety proved to be unnecessary. Molecular modelling calculations of a hit compound showed that the triazole and 2-aminopyridine rings were involved in important π-stacking interactions with Tyr178.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::4b663b337567a6bb6028ba4caa0894c9 https://doi.org/10.1002/ejoc.201403129 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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