The role of fluorine atoms in a fluorinated prostaglandin agonist

ChemMedChem

Volumn 5, Issue 8, 2010, Pages 1254-1257

  Fujimura, Ken Ichi ^a   Sasabuchi, Yoshimasa ^a  

^a SANTEN PHARMACEUTICAL CO LTD   (Japan)

Author keywords

Fluorine; Ligand design; Noncovalent interactions; Prostaglandins; Receptors

Indexed keywords

FLUORINE; PROSTAGLANDIN RECEPTOR STIMULATING AGENT;

ARTICLE; BINDING AFFINITY; DRUG STRUCTURE; FLUORINATION; PRIORITY JOURNAL; RECEPTOR BINDING;

DRUG DESIGN; FLUORINE; MOLECULAR DYNAMICS SIMULATION; PROSTAGLANDINS; PROTEIN BINDING; RECEPTORS, PROSTAGLANDIN; THERMODYNAMICS;

EID: 77955103679     PISSN: 18607179     EISSN: 18607187     Source Type: Journal    
DOI: 10.1002/cmdc.201000174     Document Type: Article

References (38)

1. S. Purser, P. R. Moore, S. Swallow, V. Gouverneur, Chem. Soc. Rev. 2008, 37, 320-330;
2. P. Shah, A. D. Westwell, J. Enzyme Inhib. Med. Chem. 2007, 22, 527-540;
3. W. K. Hagmann, J. Med. Chem. 2008, 51, 4359-4369.
4. J. C. Biffinger, H. W. Kim, S. G. DiMagno, ChemBioChem 2004, 5, 622-627.
5. T. Nakajima, T. Matsugi, W. Goto, M. Kageyama, N. Mori, Y. Matsumura, H. Hara, Biol. Pharm. Bull. 2003, 26, 1691-1695;
6. Y. Matsumura, N. Mori, T. Nakano, H. Sasakura, T. Matsugi, H. Hara, Y. Morizawa, Tetrahedron Lett. 2004, 45, 1527-1529.
7. Y. Takagi, T. Nakajima, A. Shimazaki, M. Kageyama, T. Matsugi, Y. Matsumura, B. T. Gabelt, P. L. Kaufman, H. Hara, Exp. Eye Res. 2004, 78, 767-776.
8. P. Klimko, M. Hellberg, M. McLaughlin, N. Sharif, B. Severns, G. Williams, K. Haggard, J. Liao, Bioorg. Med. Chem. 2004, 12, 3451-3469.
9. B. Resul, J. Stjernschantz, Curr. Opin. Ther. Pat. 1993, 3, 781-795; Shionogi & Co. Ltd. , (Osaka, Japan), WO9113869, 1991.
10. K. Müller, C. Faeh, F. Diedrich, Science 2007, 317, 1881-1886;
11. R. Paulini, K. Müller, F. Diedrich, Angew. Chem. 2005, 117, 1820-1839;
12. Angew. Chem. Int. Ed. 2005, 44, 1788-1805;
13. R. Paulini, K. Müller, F. Diedrich, Angew. Chem. 2005, 117, 1820-1839;
14. J. A. Olsen, D. W. Banner, P. Seiler, B. Wagner, T. Tschopp, U. O. Sander, M. Kansy, K. Müller, F. Diedrich, ChemBioChem 2004, 5, 666-675.
15. Y. Li, F. Zhu, N. Vaidehi, W. A. Goddard III, F. Sheinerman, S. Reiling, I. Morize, L. Mu, K. Harris, A. Ardati, A. Laoui, J. Am. Chem. Soc. 2007, 129, 10720.
16. F. Neuschäfer-Rube, E. Engemaier, S. Koch, U. Böer, G. P. Püschel, Biochem. J. 2003, 371, 443-449.
17. -1) of the cyclic part, 2[a], bound Thr 294 and Asn 84 through H-bonding interactions. In the other pose, 2[b], 9-OH formed a hydrogen bond with Ser 33. MD simulations (310 K, 1 ns) showed less fluctuations in 2[a] than 2[b] (table 1S in the Supporting Information).We adopted the more stably retained 2[a] as the binding pose.
18. V. L. Schuster, S. Itoh, S. W. Andrews, R. M. Burk, J. Chen, K. M. Kedzie, D. W. Gil, D. F. Woodward, Mol. Pharmacol. 2000, 58, 1511-1516.
19. 2 moiety that flipped away once from Asp77 along the ω-chain carbon skeleton after fluorine constraint removal. Compound 3[b], with a stable cyclic conformation, showed significantly more changes in the MD run (table 2S in the Supporting Information). Consequently, stable 3[a] was used.
20. αH (2.64 Å), Gln297C (3.86 Å).
21. P. Zhou, J. Zou, F. Tian, Z. Shang, J. Chem. Inf. Model. 2009, 49, 2344-2355.
22. Z. Feng, M. R. Hellberg, N. A. Sharif, M. A. McLughlin, G. W. Williams, D. Scott, T. Wallace, Bioorg. Med. Chem. 2009, 17, 576-584;
23. B. W. Griffin, P. Klimko, J. Y. Crider, N. A. Sharif, J. Pharmcol. Exp. Ther. 1999, 290, 1278-1284.
24. D. G. Fedorov, K. Kitaura, J. Comput. Chem. 2007, 28, 222-237.
25. PDB ID: 1L9H (T. Okada, Y. Fujiyoshi, M. Silow, J. Navarro, E. M. Landau, Y. Shichida, Proc. Natl. Acad. Sci. USA 2002, 99, 5982-5987);
26. PDB ID: 1FJS (M. Adler, D. D. Davey, G. B. Phillips, S. H. Kim, J. Jancarik, G. Rumennik, D. R. Light, M. Whitlow, Biochemistry 2000, 39, 12534-12542);
27. PDB ID: 1P2A (J.-J. Liu, A. Dermatakis, C. M. Lukacs, F. Konzelmann, Y. Chen, U. Kammlott, W. Depinto, H. Yang, X. Yin, Y. Chen, A. Schutt, M. E. Simcox, K.-C. Luk, Bioorg. Med. Chem. 2003, 13, 2465-2468).
28. The difference between AMBER-and FMO-optimized structures implies insufficiency of AMBER parameters with respect to covalently bound fluorine atoms.
29. K. Kitaura, E. Ikeo, T. Asada, T. Nakano, M. Uebayashi, Chem. Phys. Lett. 1999, 313, 701-706;
30. M. W. Schmidt, K. K. Baldridge, J. A. Boatz, S. T. Elbert, M. S. Gordon, J. J. Jensen, S. Koseki, N. Matsunaga, K. A. Nguyen, S. Su, T. L. Windus, M. Dupuis, J. A. Montgomery, J. Comput. Chem. 1993, 14, 1347-1363.
31. Contribution of each fluorine atom was evaluated additionally by FMO with compound 6 or 7.
32. N. A. Sharif, J. Y. Crider, T. L. Davis, J. Pharm. Pharmacol. 2000, 52, 1529-1539.
33. δ2H (∼2.2 Å), 16-F⋯Asn 44Nd2H (∼3.1 Å).
34. Modeller 9v1, Accelrys Software Inc., (San Diego, USA), 2007.
35. Membrane Builder, CHARMM-GUI, (University of Kansas, USA); http://www.charmm-gui.org/?doc=input/membrane (Last accessed: May 11, 2010).
36. D. A. Pearlman, D. A. Case, J. W. Caldwell, W. S. Ross, T. E. Cheatham, III, S. DeBolt, D. Ferguson, G. Seibel, P. Kollman, Comp. Phys. Commu. 1995, 91, 1-41;
37. D. A. Case, T. Cheatham, T. Darden, H. Gohlke, R. Luo, K. M. Merz, Jr., A. Onufriev, C. Simmerling, B. Wang, R. Woods, J. Comput. Chem. 2005, 26, 1668-1688.
38. M. Suenaga, J. Comput. Chem. Jpn. 2008, 7, 33-54.