Truncation and non-natural amino acid substitution studies on HTLV-I protease hexapeptidic inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 1, 2008, Pages 366-370

  Nguyen, Jeffrey Tri ^a   Zhang, Meihui ^a,b   Kumada, Henri Obadja ^a   Itami, Ayako ^a   Nishiyama, Keiji ^a   Kimura, Tooru ^a   Cheng, Maosheng ^b   Hayashi, Yoshio ^a,c   Kiso, Yoshiaki ^a  

^a Center for Frontier Research in Medicinal Science   (Japan)

^b SHENYANG PHARMACEUTICAL UNIVERSITY   (China)

^c TOKYO UNIVERSITY OF PHARMACY AND LIFE SCIENCES   (Japan)

Author keywords

Adult T cell leukemia; Human immunodeficiency virus; Human T cell leukemia virus; Protease inhibitor

Indexed keywords

GLUTAMINE; HEXAPEPTIDE; HISTIDINE; ISOLEUCINE; KNI 10166; KNI 10167; KNI 10168; KNI 10516; METHIONINE; PROLINE; PROTEINASE INHIBITOR; UNCLASSIFIED DRUG; VALINE;

AMINO ACID SUBSTITUTION; ARTICLE; DRUG POTENCY; DRUG SYNTHESIS; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN T CELL LEUKEMIA VIRUS 1; IC 50; INFLAMMATORY DISEASE; NONHUMAN; PARAPLEGIA; SPINAL CORD DISEASE; STRUCTURE ACTIVITY RELATION; T CELL LEUKEMIA; VIRUS INHIBITION;

AMINO ACID SUBSTITUTION; AMINO ACIDS; HUMAN T-LYMPHOTROPIC VIRUS 1; OLIGOPEPTIDES; PROTEASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY;

HUMAN IMMUNODEFICIENCY VIRUS; HUMAN T-LYMPHOTROPIC VIRUS 1;

EID: 37548998994     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2007.10.066     Document Type: Article

References (13)

1. Takatsuki K. Retrovirology 2 (2005) 16
2. Jacobson S. J. Infect. Dis. 186 Suppl. 2 (2002) S187
3. Gallo C. Retrovirology 2 (2005) 17
4. Proietti F.A., Carneiro-Proietti A.B.F., Catalan-Soares B.C., and Murphy E.L. Retrovirology 24 (2005) 6058
5. Hatanaka M., and Nam S.H. J. Cell. Biochem. 40 (1989) 15
6. Shuker S.B., Mariani V.L., Herger B.E., and Dennison K.J.. Chem. Biol. 10 (2003) 373
7. Ha J.J., Gaul D.A., Mariani V.L., Ding Y.S., Ikeda R.A., and Shuker S.B. Bioorg. Chem. 30 (2002) 138
8. Maegawa H., Kimura T., Arii Y., Matsui Y., Kasai S., Hayashi Y., and Kiso Y. Bioorg. Med. Chem. Lett. 14 (2004) 5925
9. Kimura T., Nguyen J.-T., Maegawa H., Nishiyama K., Arii Y., Matsui Y., Hayashi Y., and Kiso Y. Bioorg. Med. Chem. Lett. 17 (2007) 3276
10. 2; 8% HTLV-I PR inhibition at 600 nM; 36% HIV-1 PR inhibition at 50 nM.
11. Naka H., Teruya K., Bang J.K., Aimoto S., Tatsumi T., Konno H., Nosaka K., and Akaji K. Bioorg. Med. Chem. Lett. 16 (2006) 3761
12. A synthesized HTLV-I PR gene was introduced into Escherichia coli BL21(DE3)-pLysS cells as described in Ref. 8. The gene was extracted and mutated to construct a plasmid as follows: (1) an NdeI restriction site was added to the 5′ end; (2) the Leu40 codon was mutated to an Ile codon to block autolysis; and (3) a stop codon and a PstI restriction site were introduced 3′ to the Leu125 codon. The gene was cloned into pColdI (Takara-Bio) by using the NdeI and PstI restriction sites to afford pColdI/HTLV-I PR, and introduced into E. coli BL21 cells. Expression of the gene and ensuing procedures were performed as described in Ref. 8.
13. 50 value was calculated using a probit model.