Transformation of the marine natural product cyclotheonamide A by aqueous base. X-ray analysis of a novel ligand complexed with human α-thrombin

Tetrahedron Letters

Volumn 37, Issue 21, 1996, Pages 3667-3670

  Maryanoff, Bruce E ^a   Zhang, Han Cheng ^a   Greco, Michael N ^a   Zhang, Erli ^b   Vanderhoff Hanaver, Peggy ^b   Tulinsky, Alexander ^b  

^a R W JOHNSON PHARMACEUTICAL RES I   (United States)

^b MICHIGAN STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLOTHEONAMIDE A; ENZYME INHIBITOR; MACROCYCLIC COMPOUND; PROTEINASE INHIBITOR; THROMBIN; UNCLASSIFIED DRUG;

ARTICLE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; NUCLEAR MAGNETIC RESONANCE; PROTEIN BINDING; X RAY CRYSTALLOGRAPHY;

EID: 0029889720     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(96)00658-2     Document Type: Article

References (15)

1. (a) Fusetani, N.; Matsunaga, S.; Matsumoto, H.; Takebayashi, Y. J. Am. Chem. Soc. 1990, 112, 7053-7054.
2. (b) Hagihara, M.; Schreiber, S. L. Ibid. 1992, 114, 6570-6571.
3. (c) Maryanoff, B. E.; Qiu, X.; Padmanabhan, K. P.; Tulinsky, A.; Almond, H. R., Jr.; Andrade-Gordon, P.; Greco, M. N.; Kauffman, J. A.; Nicolaou, K. C.; Liu, A.; Brungs, P. H.; Fusetani, N. Proc. Natl. Acad. Sci. USA, 1993, 90, 8048-8052.
4. (d) Lewis, S. D.; Ng, A. S.; Baldwin, J. J.; Fusetani, N.; Naylor, A. M.; Shafer, J. A. Thromb. Res. 1993, 70, 173-190.
5. (a) Maryanoff, B. E.; Greco, M. N.; Zhang, H.-C.; Andrade-Gordon, P.; Kauffman, J. A.; Nicolaou, K. C.; Liu, A.; Brungs, P. H. J. Am. Chem. Soc. 1995, 117, 1225.
6. (b) Wipf, P.; Kim, H. J. Org. Chem. 1993, 58, 5592-5594.
7. (c) Deng, J.; Hamada, Y.; Shioiri, T.; Matsunaga, S.; Fusetani, N. Angew. Chem., Int. Ed. Engl. 1994, 33, 1729-1731.
8. (d) Bastiaans, H. M. M.; van der Baan, J. L.; Ottenheijm, H. C. J. Tetrahedron Lett. 1995, 36, 5963-5966.
9. Lee, A. Y.; Hagihara, M.; Karmacharya, R.; Albers, M. W.; Schreiber, S. L.; Clardy, J. J. Am. Chem. Soc. 1993, 115, 12619-12620.
10. Maryanoff, B. E.; Zhang, H.-C.; Greco, M. N.; Glover, K. A.; Kauffman, J. A.; Andrade-Gordon, P. BioMed. Chem. 1995, 3, 1025-1038.
11. R = 16.6 min for the new product (isolated by lyophilization), 24.9 min for CtA.
12. Skrzypczak-Jankun, E.; Carperos, V. E.; Ravichandran, K. G.; Tulinsky, A.; Westbrook, M.; Maraganore, J. M. J. Mol. Biol 1991, 221, 1379-1393.
13. Hakansson, K.; Tulinsky, A.; Abelman, M. M.; Miller, T. A.; Vlasuk, G. P.; Bergum, P. W.; LimWilby, M. S. L.; Brunck, T. K. BioMed. Chem. 1995, 3, 1009-1017.
14. On exposure of 3 to human α-thrombin at 23 °C [3 (1.5 mg; 2 μmol) in phosphate buffer (0.67 mL, pH 7.3) was added to a 1:1 glycerol-water solution of human α-thrombin (114 μL, 0.04 μmol; final concentration of 2.6 mM)], there was no loss of 3 after 5 days (HPLC). Although this indicates that 3 is not a substrate for thrombin under these conditions, the possibility of enzymic hydrolysis during cocrystallization remains since a much higher effective concentration of thrombin exists within the crystal lattice.
15. 2O or MeOH adduct ions.