Title |
Design, synthesis and efficacy of novel G protein-coupled receptor kinase 2 inhibitors
|
---|---|
Published in |
European Journal of Medicinal Chemistry, September 2013
|
DOI | 10.1016/j.ejmech.2013.08.039 |
Pubmed ID | |
Authors |
Alfonso Carotenuto, Ersilia Cipolletta, Isabel Gomez-Monterrey, Marina Sala, Ermelinda Vernieri, Antonio Limatola, Alessia Bertamino, Simona Musella, Daniela Sorriento, Paolo Grieco, Bruno Trimarco, Ettore Novellino, Guido Iaccarino, Pietro Campiglia |
Abstract |
G protein-coupled receptor kinase 2 (GRK2) is a relevant signaling node of the cellular transduction network, playing major roles in the physiology of various organs/tissues including the heart and blood vessels. Emerging evidence suggests that GRK2 is up regulated in pathological situations such as heart failure, hypertrophy and hypertension, and its inhibition offers a potential therapeutic solution to these diseases. We explored the GRK2 inhibitory activity of a library of cyclic peptides derived from the HJ loop of G protein-coupled receptor kinases 2 (GRK2). The design of these cyclic compounds was based on the conformation of the HJ loop within the X-ray structure of GRK2. One of these compounds, the cyclic peptide 7, inhibited potently and selectively the GRK2 activity, being more active than its linear precursor. In a cellular system, this peptide confirms the beneficial signaling properties of a potent GRK2 inhibitor. Preferred conformations of the most potent analog were investigated by NMR spectroscopy. |
X Demographics
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United States | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Scientists | 1 | 100% |
Mendeley readers
Geographical breakdown
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Japan | 1 | 4% |
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Unknown | 23 | 92% |
Demographic breakdown
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Researcher | 7 | 28% |
Student > Bachelor | 3 | 12% |
Student > Ph. D. Student | 3 | 12% |
Professor > Associate Professor | 3 | 12% |
Student > Master | 1 | 4% |
Other | 3 | 12% |
Unknown | 5 | 20% |
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Chemistry | 7 | 28% |
Medicine and Dentistry | 6 | 24% |
Agricultural and Biological Sciences | 3 | 12% |
Biochemistry, Genetics and Molecular Biology | 2 | 8% |
Nursing and Health Professions | 1 | 4% |
Other | 1 | 4% |
Unknown | 5 | 20% |