Author/Authors :
Michael A. Walker، نويسنده , , Timothy Johnson، نويسنده , , Zhuping Ma، نويسنده , , Jacques Banville، نويسنده , , Roger Remillard، نويسنده , , Oak Kim، نويسنده , , Yunhui Zhang، نويسنده , , Andrew Staab، نويسنده , , Henry Wong، نويسنده , , Albert Torri، نويسنده , , Himadri Samanta، نويسنده , , Zeyu Lin، نويسنده , , Carol Deminie، نويسنده , , Brian Terry، نويسنده , , Mark Krystal، نويسنده , , Nicholas Meanwell، نويسنده ,
Abstract :
Integrase is one of three enzymes expressed by HIV and represents a validated target for therapy. This study reports on the discovery of a new triketoacid-based chemotype that selectively inhibits the strand transfer reaction of HIV-integrase. SAR studies showed that the template binds to integrase in a manner similar to the diketoacid-based inhibitors. Moreover, comparison of the new chemotype to two different diketoacid templates led us to propose two aryl-binding domains in the inhibitor binding site. This information was used to design a new diketoacid template with improved activity against the enzyme.
Keywords :
AIDS , HIV-integrase , Diketoacid , Triketoacid
