Human P2Y6 receptor: Molecular modeling leads to the rational design of a novel agonist based on a unique conformational preference

Journal of Medicinal Chemistry

Volumn 48, Issue 26, 2005, Pages 8108-8111

  Costanzi, Stefano ^a   Joshi, Bhalchandra V ^a   Maddileti, Savitri ^b   Mamedova, Liaman ^a   Gonzalez Moa, Maria J ^c   Marquez, Victor E ^c   Harden, T Kendall ^b   Jacobson, Kenneth A ^a  

^a NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES   (United States)

^b UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^c NATIONAL CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2' DEOXYMETHANOCARBAURIDINE DIPHOSPHATE; PHOSPHOLIPID; PURINE P2Y6 RECEPTOR; PURINERGIC RECEPTOR STIMULATING AGENT; RIBOSE; UNCLASSIFIED DRUG; URIDINE DIPHOSPHATE;

ARTICLE; CONFORMATIONAL TRANSITION; DRUG BINDING; DRUG CONFORMATION; DRUG DESIGN; DRUG POTENCY; HUMAN; HUMAN CELL; MOLECULAR DYNAMICS; MOLECULAR MODEL; MOLECULAR RECOGNITION; MONTE CARLO METHOD;

HUMANS; LIGANDS; MODELS, MOLECULAR; MOLECULAR CONFORMATION; RECEPTORS, PURINERGIC P2; TUMOR CELLS, CULTURED; URIDINE DIPHOSPHATE;

EID: 29744445106     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm050911p     Document Type: Article

References (18)

1. Costanzi, S.; Mamedova, L.; Gao, Z.-G.; Jacobson, K. A. Architecture of P2Y nucleotide receptors: structural comparison based on sequence analysis, mutagenesis, and homology modeling. J. Med. Chem. 2004, 47, 5393-5404.
2. Boeynaems, J. M.; Communi, D.; Gonzales, N. S.; Robaye, B. Overview of the P2 receptors. Semin. Tromb. Hemost. 2005, 31, 139-149.
3. - secretion in mouse trachea. Cell. Physiol. Biochem. 2005, 16, 99-108.
4. Ohno, M.; Costanzi, S.; Kim, H. S.; Kempeneers, V.; Vastmans, K.; Herdewijn, P.; Maddileti, S.; Gao, Z.-G.; Harden, T. K.; Jacobson, K. A. Nucleotide analogues containing 2-oxa-bicyclo-[2.2.1]heptane and L-α-threofuranosyl ring systems: interactions with P2Y receptors. Bioorg. Med. Chem. 2004, 12, 5619-5630.
5. Saenger, W. Principles of nucleic acid structure; Springer-Verlag: New York, Berlin, Heidelberg, 1984; pp 9-28.
6. Jacobson, K. A.; Ji, X.-d.; Li, A. H.; Melman, N.; Siddiqui, M. A.; Shin, K. J.; Marquez, V. E.; Ravi, R. G. Methanocarba analogues of purine nucleosides as potent and selective adenosine receptor agonists. J. Med. Chem. 2000, 43, 2196-2203.
7. 6 receptors. J. Med. Chem. 2002, 45, 208-218.
8. Boyer, J. L.; Adams, M.; Ravi, R. G.; Jacobson, K. A.; Harden, T. K. Br. J. Pharmacol. 2002, 135, 2004-2010.
9. Woolf, T. B.; Roux, B. Structure, energetics, and dynamics of lipid-protein interactions: A molecular dynamics study of the gramicidin A channel in a DMPC bilayer. Proteins 1996, 24, 92-114.
10. Brooks, B. R.; Bruccoleri, R. E.; Olafson, B. D.; States, D. J.; Swaminathan, S.; Karplus, M. CHARMM - a program for macromolecular energy, minimization, and dynamics calculations. J. Comput. Chem. 1983, 4, 187-217.
11. Costanzi, S.; Vincenzetti, S.; Cristalli, G.; Vita, A. Human cytidine deaminase: a three-dimensional homology model of a tetrameric metallo-enzyme inferred from the crystal structure of a distantly related dimeric homologue. J. Mol. Graph. Model., submitted.
12. 1 receptor in surface expression and activation processes. J. Biol. Chem. 1999, 274, 14639-14647.
13. Klco, J. M.; Wiegand, C. B.; Narzinski, K.; Baranski, T. J. Essential role for the second extracellular loop in C5a receptor activation. Nat. Struct. Mol. Biol. 2005, 12, 320-326.
14. Baneres, J. L.; Mesnier, D.; Martin, A.; Joubert, L.; Dumuis, A.; Bockaert, J. Molecular characterization of a purified 5-HT4 receptor: a structural basis for drug efficacy. J. Biol. Chem. 2005, 280, 20253-20260.
15. 1 Receptor. Biochemistry 1999, 38, 3498-3507.
16. 1 receptor. Mol. Pharmacol. 1997, 52, 499-507.
17. Marquez, V. E.; Siddiqui, M. A.; Ezzitouni, A.; Russ, P.; Wang, J.; Wagner, R. W.; Matteucci, M. D. J. Med. Chem. 1996, 39, 3739-3747.
18. Ezzitouni, A.; Marquez, V. E. Conformationally locked carbocyclic nucleosides built on a bicyclo[3.1.0]hexane template with a fixed Southern conformation. Synthesis and antiviral activity. J. Chem. Soc., Perkin Trans, 1 1997, 1073-1078.