Identification of peptidomimetic HTLV-I protease inhibitors containing hydroxymethylcarbonyl (HMC) isostere as the transition-state mimic

Bioorganic and Medicinal Chemistry Letters

Volumn 14, Issue 23, 2004, Pages 5925-5929

  Maegawa, Hikoichiro ^a   Kimura, Tooru ^a   Arii, Yasuhiro ^a   Matsui, Yasuko ^a   Kasai, Soko ^a   Hayashi, Yoshio ^a   Kiso, Yoshiaki ^a  

^a KYOTO PHARMACEUTICAL UNIVERSITY   (Japan)

Author keywords

Adult T cell leukemia (ATL); Aspartic protease; Chemical ligation; Human T cell leukemia virus type I (HTLV I); Hydroxymethylcarbonyl (HMC) isostere; Inhibitor

Indexed keywords

ANTIVIRUS AGENT; CARBONYL DERIVATIVE; KNI 10159; KNI 10160; KNI 10161; KNI 10162; KNI 577; KNI 727; KNI 764; KNI 840; KYNOSTATIN 272; PEPSTATIN; PROTEINASE INHIBITOR; RITONAVIR; UNCLASSIFIED DRUG; VIRUS ENZYME;

ANTIVIRAL ACTIVITY; ARTICLE; CONTROLLED STUDY; DRUG ACTIVITY; DRUG IDENTIFICATION; DRUG POTENCY; DRUG SCREENING; DRUG SYNTHESIS; ENZYME SUBSTRATE COMPLEX; HUMAN T CELL LEUKEMIA VIRUS 1; NONHUMAN;

AMINO ACID SEQUENCE; ASPARTIC ENDOPEPTIDASES; HUMANS; MOLECULAR SEQUENCE DATA; PROTEASE INHIBITORS;

HUMAN IMMUNODEFICIENCY VIRUS; HUMAN T-LYMPHOTROPIC VIRUS 1;

EID: 7044254904     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2004.09.034     Document Type: Article

References (35)

1. Y. Hinuma, K. Nagata, M. Hanaoka, M. Nakai, T. Matsumoto, K. Kinoshita, S. Shirakawa, and I. Miyoshi Proc. Natl. Acad. Sci. U.S.A. 78 1981 6476
2. M. Osame, K. Usuku, S. Izumo, N. Ijichi, H. Amitani, A. Igata, M. Matsumoto, and M. Tara Lancet 1 1986 1031
3. A. Gessain, F. Barin, J.C. Vernant, O. Gout, L. Maurs, A. Calender, and G. De Thé Lancet 2 1985 407
4. T. Uchiyama Annu. Rev. Immunol. 15 1997 15
5. M. Osame J. Neurovirol. 8 2002 359
6. S. Oroszlan, and R.B. Luftig Curr. Top. Microbiol. Immunol. 157 1990 153
7. A. Ménard, R. Leonard, S. Rlido, S. Geoffre, P. Picard, F. Berteau, G. Precigoux, M. Hospital, and B. Guillemain FEBS Lett. 346 1994 268
8. K. Akaji, K. Teruya, and S. Aimoto J. Org. Chem. 68 2003 4755
9. C.N. Flexner Eng. J. Med. 338 1998 1281
10. Y. Kiso Biopolymers 40 1996 235
11. A. Nezami, I. Luque, T. Kimura, Y. Kiso, and E. Freire Biochemistry 41 2002 2273
12. M. Kobayashi, Y. Ohi, T. Asano, T. Hayakawa, K. Kato, A. Kakinuma, and M. Hatanaka FEBS Lett. 293 1991 106
13. Y.S. Ding, S.M. Owen, R.B. Lal, and R.A. Ikeda J. Virol. 72 1998 3383
14. J.M. Louis, S. Oroszlan, and J. Tözsér J. Biol. Chem. 274 1999 6660
15. O. Hrusková-Heidingsfeldová, I. Bláha, J. Urban, P. Strop, and I. Pichová Leukemia 11 1997 45
16. K. Teruya, T. Kawakami, K. Akaji, and S. Aimoto Tetrahedron Lett. 43 2002 1487
17. The gene was kindly provided by Prof. A. Adachi of Tokushima University
18. The cell was cultured in M9ZB medium containing 100 μg/mL ampicillin to the optical density at 600 nm of 0.6, and then the expression of the HTLV-I PR was induced by the addition of isopropyl-β-D-thiogalactopyranoside (IPTG) to a final concentration of 1 mM. The inducing culture was incubated at 37°C for 3 h
19. The supernatant was incubated with 2 mL of Ni-NTA agarose (Qiagen) for 1 h at 25°C with shaking. The Ni-NTA agarose was packed into an empty column and washed three times with 5 mL of buffer B (buffer A, pH 6.3). The protein was eluted with buffer C (buffer A, pH 4.5)
20. U.K. Laemmli Nature 227 1970 680
21. D.R. Englebretsen, B.G. Garnham, D.A. Bergman, and P.F. Alewood Tetrahedron Lett. 36 1995 8871
22. J. Méry, J. Brugidou, and J. Derancourt Pept. Res. 5 1992 233
23. J. Méry, C. Granier, M. Juin, and J. Brugidou Int. J. Peptide Protein Res. 42 1993 44
24. Y. Kiso, T. Kimura, Y. Fujiwara, N. Nishizawa, H. Matsumoto, M. Kishida, K. Akaji, and H. Takaku Peptides Frontiers Peptide Sci. 23 1999 333
25. 2: 6319.41)
26. 90: 7199.16)
27. 2: 13399.6)
28. T. Mimoto, J. Imai, S. Kisanuki, H. Enomoto, N. Hattori, K. Akaji, and Y. Kiso Chem. Pharm. Bull. 40 1992 2251
29. T. Mimoto, R. Kato, H. Takaku, S. Nojima, K. Terashima, S. Misawa, T. Fukazawa, T. Ueno, H. Sato, M. Shintani, Y. Kiso, and H. Hayashi J. Med. Chem. 42 1999 1789
30. H. Matsumoto, T. Kimura, T. Hamawaki, A. Kumagai, T. Goto, K. Sano, Y. Hayashi, and Y. Kiso Bioorg. Med. Chem. 9 2001 1589
31. S. Daenke, H.J. Schramm, and C.R.M. Bangham J. Gen. Virol. 75 1994 2233
32. 3CN containing 0.1% TFA for 12, 14 and 15 min, respectively, monitored at 215 nm. The concentration of each fragment was calculated with a standard curve
33. All inhibitors were dissolved in DMSO to make a 5 mM stock solution. Final concentrations in the inhibitor assay were 2.0 μM HTLV-I PR, 200 μM substrate (the modified p19/24), 200 mM sodium citrate buffer, pH 5.3, containing 1 mM DTT, 1 M NaCl, 5 mM EDTA, 6% glycerol and 2% DMSO containing 5 or 100 μM inhibitor at 37°C for 6 h. The residual protease activity was analyzed by the same way
34. 30 The reactions were incubated at 37°C for 30 min. The modified p19/24, APQVL*NphVMHPL, was used as a substrate
35. M. Dixon Biochem. J. 55 1953 170