Peptidic HIV integrase inhibitors derived from HIV gene products: structure-activity relationship studies.
Structure-activity relationship studies were conducted on HIV integrase (IN) inhibitory peptides which were found by the screening of an overlapping peptide library derived from HIV-1 gene products. Since these peptides located in the second helix of Vpr are considered to have an alpha-helical conformation, Glu-Lys pairs were introduced into the i and i+4 positions to increase the helicity of the lead compound possessing an octa-arginyl group. Ala-scan was also performed on the lead compound for the identification of the amino acid residues responsible for the inhibitory activity. The results indicated the importance of an alpha-helical structure for the expression of inhibitory activity, and presented a binding model of integrase and the lead compound.
Suzuki
Shintaro
S
Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062, Japan.
Maddali
Kasthuraiah
K
Hashimoto
Chie
C
Urano
Emiko
E
Ohashi
Nami
N
Tanaka
Tomohiro
T
Ozaki
Taro
T
Arai
Hiroshi
H
Tsutsumi
Hiroshi
H
Narumi
Tetsuo
T
Nomura
Wataru
W
Yamamoto
Naoki
N
Pommier
Yves
Y
Komano
Jun A
JA
Tamamura
Hirokazu
H
D000595:Amino Acid Sequence; D002460:Cell Line; D002942:Circular Dichroism; D018698:Glutamic Acid / Q000737:chemistry; D019428:HIV Integrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008239:Lysine / Q000737:chemistry; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000737:chemistry*
D019428:HIV Integrase Inhibitors; D010455:Peptides; D054325:vpr Gene Products, Human Immunodeficiency Virus; C514912:vpr protein, Human immunodeficiency virus 1; D018698:Glutamic Acid; D008239:Lysine