Columbia University

University of Michigan

University of Kentucky Research Foundation

Joanne MacDonald

Donald W Landry

Roger K Sunahara

James H Woods

John J Tesmer

Diwahar L Narasimhan

Chang-Guo Zhan

Shi-Xian Deng

Milan N Stojanovic

Young Min Kwon

Victor C Yang

Remy L Brim

Mei-Chuan Holden Ko

Tien-Yi Lee

Daquan Gao

Darko Stefanovic

Milan N Stojanovich

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 development of the first solution-phase molecular assembly comprising over 100 molecular logic gates, which more than quadruples the complexity performed by any previous system. 'MAYA-II' is a second generation molecular automaton capable of playing a complete game of tic-tac-toe against a human opponent, and encompasses 76 permissible game plays. MAYA-II is more user-friendly than MAYA-I, as it signals both players move in a two-color output system and imposes no constraints on the position of the human player's first move. MAYA-II is constructed from three classes of stem-loop controlled deoxyribozyme-based logic gates that are allosterically modulated by input oligonucleotides to produce fluorescent output signals.

Medium scale integration of molecular logic gates in an automaton

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New York, NY, United States of America

Joanne MacDonald