Monoclonal antibodies against a phencyclidine derivative are used to investigate protein-ligand interactions.
Monoclonal antibodies against the irreversible alkylator N-ethyl-1-[2-(4-isothiocyanothienyl)]cyclohexylamine (ITCE) of the 1-[1-(2-thienyl)cyclohexyl]piperidine (TCP) binding site of the N-methyl-D-aspartate receptor were raised. Each antibody was characterized in a competition enzyme-linked immunosorbent assay (ELISA) with a range of TCP analogs. It was found that each monoclonal antibody has a different affinity profile for the various TCP analogs. No correlation between the structure of the side chain groups of each compound and the selective affinities of the antibodies could be deduced, indicating that the overall affinity of the antibodies is determined by more than just the sum of the interaction forces with each ligand's functional groups. In addition to the possible identification of endogenous TCP-like compounds these antibodies could be used as a model to study the molecular interaction between drugs and their receptors' active sites.
Casalotti
S O
SO
Neuro-behavioural Biology Center, Mahidol University, Salaya, Nakorn Pathom, Thailand.
Kozikowski
A P
AP
Fauq
A
A
Tückemantel
W
W
Krueger
K E
KE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002460:Cell Line; D003514:Cyclohexylamines / Q000276:immunology; D015195:Drug Design; D004797:Enzyme-Linked Immunosorbent Assay; D017879:Isothiocyanates / Q000276:immunology; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000276:immunology* / Q000494:pharmacology; D011506:Proteins / Q000737:chemistry*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects
D000911:Antibodies, Monoclonal; D003514:Cyclohexylamines; D017879:Isothiocyanates; D008024:Ligands; D011506:Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C085267:N-ethyl-1-(2-(4-isothiocyanothienyl))cyclohexylamine; C012058:tenocyclidine; D010622:Phencyclidine