title: Positional linker effects in haptens for cocaine immunopharmacotherapy.
abstract: Cocaine use remains a serious problem, despite intensive efforts to curb abuse. Given the lack of effective pharmacotherapeutics for the treatment of cocaine addiction, research groups have targeted immunopharmacotherapy in which the drug user's immune system is trained to recognize and remove cocaine prior to entry into the central nervous system. Antibody cocaine esterases and simple binders have been procured, however, rates and/or affinities still need improvement before clinical trials are warranted. Herein, we report the synthesis and testing of two new haptens for the procurement of cocaine binding antibodies and cocaine esterase catalytic antibodies. Central in the design of these haptens was the placement of the linker functionality distal from the anticipated cocaine epitopes in an attempt to bury the hapten deep within an antibody combining site to gain possible entropic and enthalpic advantages.
authors.affiliation: Department of Chemistry, The Skaggs Institute for Chemical Biology, 10550 North Torry Pines Road, La Jolla, CA 92037, USA.
authors.forename: Akira
authors.initials: A
authors.lastname: Ino
authors.forename: Tobin J
authors.initials: TJ
authors.lastname: Dickerson
authors.forename: Kim D
authors.initials: KD
authors.lastname: Janda
mesh_terms: D019970:Cocaine-Related Disorders / Q000188:drug therapy*; D018360:Crystallography, X-Ray; D004797:Enzyme-Linked Immunosorbent Assay; D006241:Haptens / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D007167:Immunotherapy; D008958:Models, Molecular
chemical_list: D006241:Haptens