2cem
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Two series of P1'-extended HIV-1 protease inhibitors comprising a tertiary | + | Two series of P1'-extended HIV-1 protease inhibitors comprising a tertiary alcohol in the transition-state mimic exhibiting Ki values ranging from 2.1 to 93 nM have been synthesized. Microwave-accelerated palladium-catalyzed cross-couplings were utilized to rapidly optimize the P1' side chain. High cellular antiviral potencies were encountered when the P1' benzyl group was elongated with a 3- or 4-pyridyl substituent (EC50 = 0.18-0.22 microM). X-ray crystallographic data were obtained for three inhibitors cocrystallized with the enzyme. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Human immunodeficiency virus 1]] | [[Category: Human immunodeficiency virus 1]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Ekegren, J | + | [[Category: Ekegren, J K.]] |
[[Category: Ginman, N.]] | [[Category: Ginman, N.]] | ||
[[Category: Hallberg, A.]] | [[Category: Hallberg, A.]] | ||
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[[Category: protease]] | [[Category: protease]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:47:48 2008'' |
Revision as of 14:47, 21 February 2008
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P1' EXTENDED HIV-1 PROTEASE INHIBITORS ENCOMPASSING A TERTIARY ALCOHOL IN THE TRANSITION-STATE MIMICKING SCAFFOLD
Overview
Two series of P1'-extended HIV-1 protease inhibitors comprising a tertiary alcohol in the transition-state mimic exhibiting Ki values ranging from 2.1 to 93 nM have been synthesized. Microwave-accelerated palladium-catalyzed cross-couplings were utilized to rapidly optimize the P1' side chain. High cellular antiviral potencies were encountered when the P1' benzyl group was elongated with a 3- or 4-pyridyl substituent (EC50 = 0.18-0.22 microM). X-ray crystallographic data were obtained for three inhibitors cocrystallized with the enzyme.
About this Structure
2CEM is a Single protein structure of sequence from Human immunodeficiency virus 1 with as ligand. Active as HIV-1 retropepsin, with EC number 3.4.23.16 Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Microwave-accelerated synthesis of P1'-extended HIV-1 protease inhibitors encompassing a tertiary alcohol in the transition-state mimicking scaffold., Ekegren JK, Ginman N, Johansson A, Wallberg H, Larhed M, Samuelsson B, Unge T, Hallberg A, J Med Chem. 2006 Mar 9;49(5):1828-32. PMID:16509598
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