1qbr: Difference between revisions

Revision as of 15:38, 21 February 2008

HIV-1 PROTEASE INHIBITORS WIIH LOW NANOMOLAR POTENCY

OverviewOverview

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.

About this StructureAbout this Structure

1QBR 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 Full crystallographic information is available from OCA.

ReferenceReference

Cyclic urea amides: HIV-1 protease inhibitors with low nanomolar potency against both wild type and protease inhibitor resistant mutants of HIV., Jadhav PK, Ala P, Woerner FJ, Chang CH, Garber SS, Anton ED, Bacheler LT, J Med Chem. 1997 Jan 17;40(2):181-91. PMID:9003516

Page seeded by OCA on Thu Feb 21 14:37:58 2008

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OCA

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-[[Image:1qbr.gif|left|200px]]<br />
+[[Image:1qbr.gif|left|200px]]<br /><applet load="1qbr" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="1qbr" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="1qbr, resolution 1.8&Aring;" />
 '''HIV-1 PROTEASE INHIBITORS WIIH LOW NANOMOLAR POTENCY'''<br />
 ==Overview==
-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.
+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.
 ==About this Structure==
-QBR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with XV6 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1QBR OCA].
+QBR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with <scene name='pdbligand=XV6:'>XV6</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QBR OCA].
 ==Reference==
@@ Line 16: / Line 15: @@
 [[Category: Single protein]]
 [[Category: Ala, P.]]
-[[Category: Chang, C.H.]]
+[[Category: Chang, C H.]]
 [[Category: XV6]]
 [[Category: aspartyl protease]]
 [[Category: hydrolase (acid proteinase)]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Thu Nov  8 14:23:56 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:37:58 2008''