Targeting of HIV gp120 by oligonucleotide-photosensitizer conjugates. Light-induced damages.
Some guanine-rich oligonucleotides inhibit HIV infectivity through interaction with the gp120 glycoprotein. Besides, photoinactivation of viruses attracts attention for blood decontamination. The feasibility of targeting a red light-absorbing chlorin-type photosensitizer to gp120 through covalent coupling with 8-mer phosphodiester oligodeoxynucleotides is investigated. Some conjugates inhibit binding of antibodies directed to gp120. Inhibition is significantly increased upon red light activation. The activity of the conjugates correlates with their ability to self-associate, a process strongly favored by the propensity of the hydrophobic chlorin moiety to dimerize. Thus, the photosensitizer moiety both promotes structures with a higher affinity for gp120 and, upon light activation, can induce site-directed damages to the protein.
Vever-Bizet
C
C
Laboratoire de Photobiologie, Muséum National d'Histoire Naturelle, INSERM U 201, CNRS UMR 8646, Paris, France.
Boutorine
A S
AS
Delgado
O
O
Brault
D
D
Hélène
C
C
D000595:Amino Acid Sequence; D019281:Dimerization; D004307:Dose-Response Relationship, Radiation; D004797:Enzyme-Linked Immunosorbent Assay; D015699:HIV Envelope Protein gp120 / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000528:radiation effects; D008027:Light; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000378:metabolism / Q000494:pharmacology*; D010787:Photosensitivity Disorders; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000494:pharmacology* / Q000502:physiology
C403362:CHEVP, oligonucleotide; D015699:HIV Envelope Protein gp120; D009841:Oligonucleotides; D017319:Photosensitizing Agents; D011166:Porphyrins; C006969:chlorin