A tetradecapeptide somatostatin dicarba-analog: Synthesis,structural impact and biological activity |
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| Institution: | 1. Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac, 10, 08028 Barcelona, Spain;2. Departament de Química Orgànica, Universitat de Barcelona, Martí i Franqués, 1-11, 08028 Barcelona, Spain;3. Institució Catalana de Recerca i Estudis Avançats (ICREA), Passeig Lluis Companys, 23, 08010 Barcelona, Spain;4. BCN Peptides S.A. Pol.Ind. Els Vinyets-Els Fogars, Sector II. Ctra. Comarcal 244, Km. 22. Sant Quintí de Mediona, 08777 Barcelona, Spain;5. Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Alcalá de Henares, 28871 Madrid, Spain;1. Johann Wolfgang Goethe University, Institute of Pharmaceutical Chemistry, Biozentrum, Max-von-Laue-Str. 9, 60438 Frankfurt/Main, Germany;2. Heinrich Heine University Duesseldorf, Institute of Pharmaceutical and Medicinal Chemistry, Universitaetsstr. 1, 40225 Duesseldorf, Germany;1. Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi ‘Aldo Moro’ di Bari, Via Orabona 4, 70126 Bari, Italy;2. Università degli Studi di Firenze, Dipartimento di Chimica, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy;3. Università degli Studi di Firenze, Neurofarba Dept., Section of Pharmaceutical and Nutriceutical Sciences, Via U. Schiff 6, 50019 Sesto Fiorentino (Firenze), Italy;1. Silvio O. Conte Center for Oxytocin and Social Cognition, Center for Translational Social Neuroscience, Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30329, USA;2. Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA 30322, USA;3. Department of Psychology, University of California, Davis, CA 95616, USA;4. Department of Medical Physics, University of Wisconsin, Madison, WI 53705, USA;5. Department of Obstetrics and Gynecology and Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, USA;6. Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin, Madison, WI 53715, USA;7. Center for Molecular and Genomic Imaging, University of California, Davis, CA 95616, USA;1. Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA;2. Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, USA;3. Vanderbilt Specialized Chemistry Center for Probe Development (MLPCN), Nashville, TN 37232, USA;4. Department of Chemistry, Vanderbilt University, Nashville, TN 37232, USA;5. Vanderbilt Institute of Chemical Biology, Vanderbilt University/Vanderbilt University Medical Center, Nashville, TN 37232, USA |
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| Abstract: | We described here the first tetradecapeptide somatostatin-analogue where the disulfide bridge has been replaced by a carbon–carbon double bond. This analogue was prepared using microwave assisted ring closing metathesis (RCM) using the 2nd generation Grubbs as catalyst. Under our optimized conditions the cyclization between allylGly 3 and 14 proceeded in moderate yield, excellent cyclic/linear ratio and very high Z-double bond selectivity. NMR studies also demonstrated that the conformational flexibility of this peptide is increased in comparison to that of the natural hormone. Remarkably, this alkene-bridged somatostatin analog is highly selective against somatostatin receptors 1 and 5, suggesting that conformational rigidity is not required for the efficient interaction of somatostatin analogues with these two receptors. |
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| Keywords: | Somatostatin Ring-closing metathesis NMR studies Peptide analogs |
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