SAR study and conformational analysis of a series of novel peptide G protein‐coupled receptor kinase 2 inhibitors. Issue 1 (25th October 2013)

• Record Type: Journal Article
• Authors: Gomez‐Monterrey, Isabel; Carotenuto, Alfonso; Cipolletta, Ersilia; Sala, Marina; Vernieri, Ermelinda; Limatola, Antonio; Bertamino, Alessia; Musella, Simona; Grieco, Paolo; Trimarco, Bruno; Novellino, Ettore; Iaccarino, Guido; Campiglia, Pietro
• Is Part Of: Biopolymers. Volume 101:Issue 1(2014)
• Page Start: 121
• Page End: 128
• Publication Date: 2013-10-25
• Subjects: Biopolymers -- Periodicals; Peptides -- Periodicals; Spectrum analysis -- Periodicals; 572.33
• DOI: 10.1002/bip.22295
• Languages: English
• ISSNs: 0006-3525

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <p>G protein‐coupled receptor kinase 2 (GRK2) plays a central role in the cellular transduction network. In particular, during chronic heart failure GRK2 is upregulated and believed to contribute to disease progression. Thereby, its inhibition offers a potential therapeutic solution to several pathological conditions. In the present study, we performed a SAR study and a NMR conformational analysis of peptides derived from HJ loop of GRK2 and able to selectively inhibit GRK2. From Ala‐scan and <sc>d</sc>‐Ala point replacement, we found that Arg residues don't affect the inhibitory properties, while a <sc>d</sc>‐amino acid at position 5 is key to the activity. Conformational analysis identified two β‐turns that involve N‐terminal residues, followed by a short extended region. These information can help the design of peptides and peptido‐mimetics with enhanced GRK2 inhibition properties. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 121–128, 2014.</p> </abstract>