A retro-inverso miniantibody with anti-HIV activity.
An HIV-1-specific miniantibody, a peptide representing the third heavy chain complementarity-determining region (CDR) of an HIV-specific mouse antibody, was characterized and modified with unnatural D-isomeric amino acids. The CDR peptide and its parent antibody bound to a similar epitope, located in the V3 region of HIV-1 gp120. A shortened CDR sequence was modified with D-amino acids to create an all-D-amino acid retro-inverso (RI) peptide with a reversed sequence order. The RI CDR was less susceptible to proteolytic degradation than its L-counterpart and had a higher affinity for HIV-1 peptides. The miniantibody and its parent antibody showed neutralization of both primary and laboratory strains of HIV-1. In accordance with the binding studies, the RI CDR showed a stronger HIV-inhibiting capacity than its L-counterpart. We conclude that the anti-HIV retro-inverso CDR identified in this study has the potential to become a future anti-HIV drug. It has a virus-neutralizing capacity in vitro and appears to be stable. Future research should focus on characterizing its antiviral activity in vivo.
Levi
M
M
Department of Virology, Swedish Institute for Infectious Disease Control and Karolinska Institute, Solna. michael.levi@smi.ki.se
Hinkula
J
J
Wahren
B
B
D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000378:metabolism; D000818:Animals; D002874:Chromosome Mapping; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*
D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D007135:Immunoglobulin Variable Region; D010446:Peptide Fragments; D000626:Aminopeptidases