Small molecular CD4 mimics as HIV entry inhibitors.
Derivatives of CD4 mimics were designed and synthesized to interact with the conserved residues of the Phe43 cavity in gp120 to investigate their anti-HIV activity, cytotoxicity, and CD4 mimicry effects on conformational changes of gp120. Significant potency gains were made by installation of bulky hydrophobic groups into the piperidine moiety, resulting in discovery of a potent compound with a higher selective index and CD4 mimicry. The current study identified a novel lead compound 11 with significant anti-HIV activity and lower cytotoxicity than those of known CD4 mimics.
Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo, Japan.
Tetsuo
T
Narumi
Hiroshi
H
Arai
Kazuhisa
K
Yoshimura
Shigeyoshi
S
Harada
Wataru
W
Nomura
Shuzo
S
Matsushita
Hirokazu
H
Tamamura
D040761:Biomimetic Materials / Q000737:chemistry* / Q000494:pharmacology; D015704:CD4 Antigens / Q000737:chemistry* / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000378:metabolism; D023581:HIV Fusion Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D023581:HIV Fusion Inhibitors