Incorporation of the Unusual Cα-Fluoroalkylamino Acids into Cyclopeptides: Synthesis of Arginine−Glycine−Aspartate (RGD) Analogues and Study of Their Conformational and Biological Behavior
| العنوان: | Incorporation of the Unusual Cα-Fluoroalkylamino Acids into Cyclopeptides: Synthesis of Arginine−Glycine−Aspartate (RGD) Analogues and Study of Their Conformational and Biological Behavior |
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| المؤلفون: | Claudio Pisano, Giuseppe Giannini, Massimo Castorina, Roberto de Castiglione, Alma Dal Pozzo, Rosanna Mondelli, Sergio Penco, Minghong Ni, Laura Muzi, Stefania Mazzini |
| المصدر: | Journal of Medicinal Chemistry. 49:1808-1817 |
| بيانات النشر: | American Chemical Society (ACS), 2006. |
| سنة النشر: | 2006 |
| مصطلحات موضوعية: | Models, Molecular, Integrins, Magnetic Resonance Spectroscopy, Arginine, Stereochemistry, Molecular Conformation, Backbone conformation, Ring (chemistry), Peptides, Cyclic, High-performance liquid chromatography, Structure-Activity Relationship, Molecular dynamics, Drug Discovery, Dimethyl Sulfoxide, Receptors, Vitronectin, Amino Acids, Chemistry, Diastereomer, Water, Stereoisomerism, Fluorine, Integrin alphaVbeta3, In vitro, Glycine, Molecular Medicine, Oligopeptides |
| الوصف: | A series of six arginine-glycine-aspartate (RGD) cyclopeptide analogues containing a C(alpha)-di- or trifluoromethylamino acid (alpha-Dfm or alpha-TfmAaa) at different positions of the ring were synthesized. All peptides were obtained in two diastereomeric forms, which were separated by HPLC. In vitro biological tests of the new cyclopeptides P were carried out in comparison with their corresponding cyclopeptides R lacking the alpha-fluoromethyl group. Five out of the six compounds P-I (containing (S)-alpha-Tfm-Aaa) showed activities in the nanomolar range, while the P-II compounds (containing (R)-alpha-Tfm-Aaa) were much less active or totally inactive. Only cyclo[RGDf-(S)-alphaTfmV] (P1-I) was found to be significantly more active than its model compound cyclo(RGDfV) (R1). The three-dimensional structure in water and DMSO was determined by NMR techniques and molecular dynamics (MD) calculations, but it was not possible to highlight significant differences in the backbone conformation of the peptides examined. Significant interproton distances, derived from nuclear Overhauser effect (NOE) experiments, were used to determine the absolute configuration of the side chains. |
| تدمد: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm0511334 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::24bfadf1cedcee28cffcbc1d22e2f627 https://doi.org/10.1021/jm0511334 |
| رقم الانضمام: | edsair.doi.dedup.....24bfadf1cedcee28cffcbc1d22e2f627 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15204804 00222623 |
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| DOI: | 10.1021/jm0511334 |