Maintaining potent HTLV-I protease inhibition without the P₃-cap moiety in small tetrapeptidic inhibitors

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• 作者：Jeffrey-Tri Nguyen^a ; Keiko Kato^a ; Henri-Obadja Kumada^a ; Koushi Hidaka^a ; Tooru Kimura^a ; Yoshiaki Kiso ; ^a ; ^{kiso@mb.kyoto-phu.ac.jp}
• 关键词：Human T cell lymphotropic virus ; Adult T cell leukemia ; Aspartic protease ; Inhibitor ; Retrovirus
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2011
• 出版时间：15 March 2011
• 年：2011
• 卷：21
• 期：6
• 页码：1832-1837
• 全文大小：434 K

文摘

The human T cell lymphotropic/leukemia virus type 1 (HTLV-I) causes adult T cell lymphoma/leukemia. The virus is also responsible for chronic progressive myelopathy and several inflammatory diseases. To stop the manufacturing of new viral components, in our previous reports, we derived small tetrapeptidic HTLV-I protease inhibitors with an important amide-capping moiety at the P₃ residue. In the current study, we removed the P₃-cap moiety and, with great difficulty, optimized the P₃ residue for HTLV-I protease inhibition potency. We discovered a very potent and small tetrapeptidic HTLV-I protease inhibitor (KNI-10774a, IC₅₀ = 13 nM).