Design, synthesis and evaluation of peptide libraries as potential anti-HIV compounds, via inhibition of gp120/cell membrane interactions, using the gp120/cd4/fab17 crystal structure.
The crystal structure of a gp120/CD4/Fab17b complex was analysed leading to the design of several peptide libraries in the hope of obtaining novel gp120/cell membrane receptor interaction inhibitors, especially inhibitors of gp120/CD4 and gp120/chemokine receptor interactions. Syntheses of tri- and tetra- and pentapeptides were performed via a solid phase synthesis methodology using a Rink Amide MBHA resin and a Fmoc strategy giving C-terminal amide form peptides. Compounds were assayed against C8166 cells infected by HIV-1 IIIB and screened using a gp120 binding assay and the FIGS reporter gene assay.
Boussard
Cyrille
C
Welsh School of Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, CF10 3XF, Cardiff, UK.
Doyle
Valerie E
VE
Mahmood
Naheed
N
Klimkait
Thomas
T
Pritchard
Martyn
M
Gilbert
Ian H
IH
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites; D015704:CD4 Antigens / Q000737:chemistry; D002459:Cell Fusion; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects; D015195:Drug Design; D004797:Enzyme-Linked Immunosorbent Assay; D015699:HIV Envelope Protein gp120 / Q000737:chemistry*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry; D020128:Inhibitory Concentration 50; D019151:Peptide Library; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D007140:Immunoglobulin Fab Fragments; D019151:Peptide Library; D010455:Peptides