1QBT

HIV-1 PROTEASE INHIBITORS WIIH LOW NANOMOLAR POTENCY

Summary for 1QBT

• Entry DOI: 10.2210/pdb1qbt/pdb
• Descriptor: HIV-1 PROTEASE, [4R-(4ALPHA,5ALPHA,6ALPHA,7ALPHA)]-3,3'-{{TETRAHYDRO-5,6-DIHYDROXY-2-OXO-4,7-BIS(PHENYLMETHYL)-1H-1,3-DIAZEPINE-1,3(2H)-DIYL]BIS(METHYLENE)]BIS[N-1H-BENZIMIDAZOL-2-YLBENZAMIDE] (2 entities in total)
• Functional Keywords: hydrolase (acid proteinase), aspartyl protease
• Biological source: Human immunodeficiency virus 1
• Cellular location: Gag-Pol polyprotein: Host cell membrane; Lipid-anchor . Matrix protein p17: Virion membrane; Lipid- anchor . Capsid protein p24: Virion . Nucleocapsid protein p7: Virion . Reverse transcriptase/ribonuclease H: Virion . Integrase: Virion : P04585
• Total number of polymer chains: 2
• Total formula weight: 22340.25

Authors

Ala, P.,Chang, C.-H. (deposition date: 1997-04-25, release date: 1997-10-15, Last modification date: 2024-02-14)

Primary citation

Jadhav, P.K.,Ala, P.,Woerner, F.J.,Chang, C.H.,Garber, S.S.,Anton, E.D.,Bacheler, L.T.
Cyclic urea amides: HIV-1 protease inhibitors with low nanomolar potency against both wild type and protease inhibitor resistant mutants of HIV.
J.Med.Chem., 40:181-191, 1997

PubMed Abstract: Cyclic urea amides, a novel series of HIV-1 protease (HIV PR) inhibitors, have increased activity against drug-resistant mutants of the HIV PR. The design strategy for these inhibitors is based on the hypotheses that (i) the hydrogen-bonding interactions between the inhibitor and the protease backbone will remain constant for wild-type and mutant enzymes and (ii) inhibitors which are capable of forming many nonbonded interactions, distributed throughout the active site, will experience a lower percent change in binding energy as a result of mutation in the target enzyme than those that form fewer interactions by partial occupation of the active site. The cyclic urea amide, SD146, forms 14 hydrogen bonds and 191 van der Waals contacts to HIV PR. SD146 is a very potent antiviral agent (IC90 = 5.1 nM) against wild-type HIV and maintains the same or improved level of high potency against a range of mutant strains of HIV with resistance to a wide variety of HIV protease inhibitors.

PubMed: 9003516
DOI: 10.1021/jm960586t

Experimental method

X-RAY DIFFRACTION (2.1 Å)