Merck + Co., Inc.

Merial Limited

The State University of New York

Jeffrey W Warmke

Doris F Cully

Michel J Hamelin

Youfeng Yang

Leonardus H Van Der Ploeg

Linda M Hall

Joseph P Arena

Ken K Liu

Guoping Feng

Peiyi Wang

Leonardus H T Van Der Ploeg

Philip S Paress

Richard Brochu

Adrian Etter

Charles J Cohen

The present invention relates in part to isolated nucleic acid molecules (polynucleotides) which encodeglutamate gated chloride channels. The present invention also relates to recombinant vectors and recombinant hosts which contain a DNA fragment encodingglutamate gated chloride channels, substantially purified forms of associatedglutamate gated chloride channels and recombinant membrane fractions comprising these proteins, associated mutant proteins, and methods associated with identifying compounds which modulate associatedglutamate gated chloride channels, which will be useful as insecticides.

[object Object]

The present invention relates in part to isolated nucleic acid molecules (polynucleotides) which encode(grasshopper) glutamate-gated chloride channels. The present invention also relates to recombinant vectors and recombinant hosts which contain a DNA fragment encodingglutamate-gated chloride channels, substantially purified forms of associatedglutamate-gated chloride channels and recombinant membrane fractions comprising these proteins, associated mutant proteins, and methods associated with identifying compounds which modulate associatedglutamate-gated chloride channels, which will be useful as insecticides.

DNAs encoding voltage-activated cation channels have been cloned and characterized. The cDNA's have been expressed in recombinant host cells which produce active recombinant protein. The recombinant protein is also purified from the recombinant host cells. In addition, the recombinant host cells are utilized to establish a method for identifying modulators of the channel activity, and channel modulators are identified. Channel modulators are useful as insecticides and arachnicidic agents.

To date, L-glutamate-gated chloride (GluCl) channels have been observed only in invertebrate organisms. Modulators of this channel (either agonists or antagoinists) will interfere with neurotransmission. For example, agents such as avermectins activate the GluCl, causing paralysis due to blocking of neurotranmitter release, resulting in death of the organism. Because GluCl channels are invertebreate specific, they are excellent targets for the discovery of novel insecticides, anthelminths and parasiticides that will display a marked safety profile because of the lack of mechanism based toxicity in vertebrate organisms. The present specification discloses isolation of a cDNA clone from the cat flea (CfGluCl-1) that encodes a L-glutamate-gated chloride channel. Heterologous expression of CfGluCl-1 cRNA in results in robust expression of a L-glutamate-gated chloride current and the channel is activated and potentiated by avermectins. The expression of CfGluCl-1 in a heterologous expression system if useful to screens for novel GluCl channel agonsts and antagonsits. Additionally, this specification disclose impoved methods of screening for GluCl channel modulators.

DNA molecules encoding Ctenocephalides felis glutamate gated chloride channels

DNAs encoding voltage-activated cation channels have been cloned and characterized. The cDNA's have been expressed in recombinant host cells which produce active recombinant protein. The recombinant protein is also purified from the recombinant host cells.

Process for functional expression of the para cation channel

Process for identifying para cation channel modulators

Growing community of inventors

Edison, NJ, United States of America

Jeffrey W Warmke