CD4 mimics targeting the HIV entry mechanism and their hybrid molecules with a CXCR4 antagonist.
Small molecules behaving as CD4 mimics were previously reported as HIV-1 entry inhibitors that block the gp120-CD4 interaction and induce a conformational change in gp120, exposing its co-receptor-binding site. A structure-activity relationship (SAR) study of a series of CD4 mimic analogs was conducted to investigate the contribution from the piperidine moiety of CD4 mimic 1 to anti-HIV activity, cytotoxicity, and CD4 mimicry effects on conformational changes of gp120. In addition, several hybrid molecules based on conjugation of a CD4 mimic analog with a selective CXCR4 antagonist were also synthesized and their utility evaluated.
Narumi
Tetsuo
T
Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062, Japan.
Ochiai
Chihiro
C
Yoshimura
Kazuhisa
K
Harada
Shigeyoshi
S
Tanaka
Tomohiro
T
Nomura
Wataru
W
Arai
Hiroshi
H
Ozaki
Taro
T
Ohashi
Nami
N
Matsushita
Shuzo
S
Tamamura
Hirokazu
H
D040761:Biomimetic Materials / Q000737:chemistry* / Q000378:metabolism; D015704:CD4 Antigens / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000378:metabolism; D023581:HIV Fusion Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D006801:Humans; D010880:Piperidines / Q000737:chemistry; D011485:Protein Binding; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D023581:HIV Fusion Inhibitors; D010880:Piperidines; D019718:Receptors, CXCR4; C514793:gp120 protein, Human immunodeficiency virus 1; C032727:piperidine