Analysis of the interaction of an anti-HIV peptide, T22 ([Tyr5, 12, Lys7]-polyphemusin II), with gp120 and CD4 by surface plasmon resonance.
We have previously found that T22 ([Tyr5, 12, Lys7]-polyphemusin II) exhibits strong anti-human immunodeficiency virus (HIV) activity comparable to that of 3'-azido-2', 3'-dideoxythymidine (AZT). The inhibition mechanism of T22 on HIV-replication has not been elucidated precisely yet, and hence the target molecules of T22 have not been identified. However, our recent research suggested that T22 exerts its effect by blocking virus-cell fusion at an early stage of HIV infection and that T22 might interact with an HIV envelope protein and/or a T-cell surface protein, both of which are critical for HIV infection. In this paper we demonstrated that T22 binds specifically to both gp120 (an envelope protein of HIV) and CD4 (a T-cell surface protein) and that both bindings can be inhibited by an anti-T22 antibody, using biosensor technology (BIAcoreTM) based on the principles of surface plasmon resonance. Linearization by the BIAcoreTM system (BIAlogue software) and nonlinear least squares analysis by curve fitting with exponential equations showed that both interactions have close dissociation constants (approximately 10(-7) M). The present study suggests that T22 inhibits the virus-cell fusion process through binding to both gp120 and CD4.
Tamamura
H
H
Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Ishihara
T
T
Otaka
A
A
Murakami
T
T
Ibuka
T
T
Waki
M
M
Matsumoto
A
A
Yamamoto
N
N
Fujii
N
N
D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000378:metabolism / Q000494:pharmacology*; D000906:Antibodies / Q000276:immunology / Q000378:metabolism; D023181:Antimicrobial Cationic Peptides; D015374:Biosensing Techniques; D015704:CD4 Antigens / Q000378:metabolism*; D006678:HIV / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D007700:Kinetics; D008561:Membrane Fusion / Q000187:drug effects; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding
D019380:Anti-HIV Agents; D000906:Antibodies; D023181:Antimicrobial Cationic Peptides; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D008565:Membrane Proteins; D010455:Peptides; C076963:T22 protein, synthetic