Modulating Cocaine Vaccine Potency through Hapten Fluorination

• Published in: Journal of the American Chemical Society Vol. 135; no. 8; pp. 2971 - 2974
• Main Authors: Cai, Xiaoqing, Tsuchikama, Kyoji, Janda, Kim D
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 27.02.2013; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Multidisciplinary; Cocaine - immunology; Fluorine - chemistry; Haptens; Physical Sciences; Science & Technology; Vaccines - immunology; MEDICINAL CHEMISTRY; ANTIBODIES; EFFICACY; ABUSE; ANALOGS; AMINO-ACIDS; DERIVATIVES; DEPENDENCE; STRATEGIES; ANTIGEN
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja400356g

Cocaine addiction is a long-lasting relapsing illness characterized by cycles of abuse, abstinence, and reinstatement, and antibody-based therapies could be a powerful therapeutic approach. Herein, we explored the possibility of using halogenated cocaine haptens to enhance the immunological properties of anti-cocaine vaccines. Three fluorine-containing cocaine haptens (GNF, GNCF and GN5F) and one chlorine-containing cocaine hapten (GNCl) were designed and synthesized, based upon the chemical scaffold of the only hapten that has reached clinical trials, succinyl norcocaine (SNC). Hapten GNF was found to retain potent cocaine affinity, and also elicit antibodies in a higher concentration than the parent structure SNC. Our data suggests that not only could strategic hapten fluorination be useful for improving upon the current cocaine vaccine undergoing clinical trials, but it may also be a valuable new approach, with application to any of the vaccines being developed for the treatment of drugs of abuse.