1G2K

HIV-1 PROTEASE WITH CYCLIC SULFAMIDE INHIBITOR, AHA047

1G2K の概要

• エントリーDOI: 10.2210/pdb1g2k/pdb
• 関連するPDBエントリー: 1ajv 1ajx
• 分子名称: PROTEASE RETROPEPSIN, 3-(7-BENZYL-4,5-DIHYDROXY-1,1-DIOXO-3,6-BIS-PHENOXYMETHYL-1L6-[1,2,7]THIADIAZEPAN-2-YLMETHYL)-N-METHYL-BENZAMIDE (3 entities in total)
• 機能のキーワード: hiv, protease inhibitors, hydrolase
• 由来する生物種: Human immunodeficiency virus 1
• 細胞内の位置: Matrix protein p17: Virion (Potential). Capsid protein p24: Virion (Potential). Nucleocapsid protein p7: Virion (Potential). Reverse transcriptase/ribonuclease H: Virion (Potential). Integrase: Virion (Potential): P04587
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22239.25

構造登録者

Lindberg, J.,Unge, T. (登録日: 2000-10-20, 公開日: 2001-06-01, 最終更新日: 2023-08-09)

主引用文献

Schaal, W.,Karlsson, A.,Ahlsen, G.,Lindberg, J.,Andersson, H.O.,Danielson, U.H.,Classon, B.,Unge, T.,Samuelsson, B.,Hulten, J.,Hallberg, A.,Karlen, A.
Synthesis and comparative molecular field analysis (CoMFA) of symmetric and nonsymmetric cyclic sulfamide HIV-1 protease inhibitors.
J.Med.Chem., 44:155-169, 2001

PubMed Abstract: We have previously reported on the unexpected flipped conformation in the cyclic sulfamide class of inhibitors. An attempt to induce a symmetric binding conformation by introducing P2/P2' substituents foreseen to bind preferentially in the S2/S2' subsite was unsuccessful. On the basis of the flipped conformation we anticipated that nonsymmetric sulfamide inhibitors, with P2/P2' side chains modified individually for the S1' and S2 subsites, should be more potent than the corresponding symmetric analogues. To test this hypothesis, a set of 18 cyclic sulfamide inhibitors (11 nonsymmetric and 7 symmetric) with different P2/P2' substituents was prepared and evaluated in an enzyme assay. To rationalize the structure-activity relationship (SAR) and enable the alignment of the nonsymmetric inhibitors, i.e., which of the P2/P2' substituents of the nonsymmetric inhibitors interact with which subsite, a CoMFA study was performed. The CoMFA model, constructed from the 18 inhibitors in this study along with seven inhibitors from previous work by our group, has successfully been used to rationalize the SAR of the cyclic sulfamide inhibitors. Furthermore, from the information presented herein, the SAR of the cyclic sulfamide class of inhibitors seems to differ from the SAR of the related cyclic urea inhibitors reported by DuPont and DuPont-Merck.

PubMed: 11170625
DOI: 10.1021/jm001024j

実験手法

X-RAY DIFFRACTION (1.95 Å)