UNEXPECTED BINDING MODE OF A CYCLIC SULFAMIDE HIV-1 PROTEASE INHIBITOR

Two cyclic, C-2-symmetric HIV-1 protease inhibitors, one sulfamide and one urea derivative, both comprising phenyl ether groups in the P1/P1 ' positions were cocrystallized with HIV-1 protease, and the crystal s tructures were determined to 2.0 Angstrom resolution. The structure of the urea 2 showed a conformation similar to that reported for the rel ated urea 3 by Lam et al., while the sulfamide 1 adopted an unanticipa ted conformation in which the P1' and P2' side chains were transposed.