Title |
SAR study and conformational analysis of a series of novel peptide G protein‐coupled receptor kinase 2 inhibitors
|
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Published in |
Biospectroscopy, October 2013
|
DOI | 10.1002/bip.22295 |
Pubmed ID | |
Authors |
Isabel Gomez‐Monterrey, Alfonso Carotenuto, Ersilia Cipolletta, Marina Sala, Ermelinda Vernieri, Antonio Limatola, Alessia Bertamino, Simona Musella, Paolo Grieco, Bruno Trimarco, Ettore Novellino, Guido Iaccarino, Pietro Campiglia |
Abstract |
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 d-Ala point replacement, we found that Arg residues don't affect the inhibitory properties, while a d-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. |
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Professor > Associate Professor | 3 | 20% |
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Researcher | 1 | 7% |
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Computer Science | 1 | 7% |
Other | 0 | 0% |
Unknown | 5 | 33% |