University of Michigan

Columbia University

University of Kentucky Research Foundation

Diwahar L Narasimhan

Roger K Sunahara

James H Woods

Donald W Landry

John J Tesmer

Joanne MacDonald

Chang-Guo Zhan

Shi-Xian Deng

Young Min Kwon

Victor C Yang

Remy L Brim

Daquan Gao

Tien-Yi Lee

Mei-Chuan Holden Ko

Milan N Stojanovic

John J G Tesmer

Milan N Stojanovich

Mark R Nance

Elin Edwald

Joanne Macdonald

Victor Yang

Provided are compositions comprising a cocaine esterase (CocE) and a compound that thermostabilizes the CocE. Also provided are methods of thermostabilizing a cocaine esterase. Additionally provided are methods of treating a mammal undergoing a cocaine-induced condition. Methods of determining whether a compound is a thermostabilizing agent for a protein are also provided. Uses of the above-described compositions for the treatment of a cocaine-induced condition is additionally provided. Additionally provided is an isolated nucleic acid encoding a CocE polypeptide having the substitutions L169K and G173Q, and the CocE polypeptide encoded by that nucleic acid, and pharmaceutical compositions thereof. Further provided is the use of that composition for the manufacture of a medicament for the treatment of a cocaine-induced condition and for the treatment of a cocaine-induced condition.

Thermostabilization of proteins

Embodiments of the invention disclosed herein generally relate to anti-cocaine therapeutics. Specifically, some embodiments of the invention relate to highly efficient, thermostable, and long-lasting cocaine esterase (CocE) mutants that can protect against the toxic and reinforcing effects of cocaine in subjects. Provided herein are mutant CocE polypeptides displaying thermostable esterase activity. Also provided are methods of treating cocaine-induced conditions in a subject in need via administration of mutant CocE as well as methods for high-throughput screening of candidate esterase polypeptides.

Anti-cocaine compositions and treatment

The present invention relates to compositions and methods for treating and preventing cocaine addiction. In particular, the present invention provides mutated cocaine esterase proteins for use in treating and preventing cocaine addiction.

Compositions and methods for altering cocaine esterase activity

Growing community of inventors

Ann Arbor, MI, United States of America

Diwahar L Narasimhan