Identification of optimal anion spacing for anti-HIV activity in a series of cosalane tetracarboxylates.
The binding of the anti-HIV agent cosalane to CD4 is thought to involve ionic interactions of negatively charged carboxylates of the ligand with positively charged residues on the surface of the protein. An investigation of the optimal anion distances for anti-HIV activity in a series of cosalane tetracarboxylate analogues has been completed, and maximal activity results when the two proximal and the two distal carboxylates are separated by eight atoms.
Paul
G C
GC
Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, IN 47907, USA.
De Clercq
E
E
Pannecouque
C
C
Witvrouw
M
M
Loftus
T L
TL
Turpin
J A
JA
Buckheit
R W
RW
Cushman
M
M
D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D001312:Aurintricarboxylic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D015704:CD4 Antigens / Q000378:metabolism; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects; D015498:HIV-2 / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D015704:CD4 Antigens; D002264:Carboxylic Acids; C083060:cosalane; D001312:Aurintricarboxylic Acid