Drug target validation: Lethal infection blocked by inducible peptide | Zendy

Jianshi Tao | Zendy; Philip A. Wendler | Zendy; Gene Connelly | Zendy; Audrey Lim | Zendy; Jiansu Zhang | Zendy; Megan King | Zendy; Tongchuan Li | Zendy; Jared Silverman | Zendy; Paul Schimmel | Zendy; Francis P. Tally | Zendy

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Drug target validation: Lethal infection blocked by inducible peptide

Author(s) -

Jianshi Tao,

Philip A. Wendler,

Gene Connelly,

Audrey Lim,

Jiansu Zhang,

Megan King,

Tongchuan Li,

Jared Silverman,

Paul Schimmel,

Francis P. Tally

Publication year - 2000

Publication title -

proceedings of the national academy of sciences

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 5.011

H-Index - 771

eISSN - 1091-6490

pISSN - 0027-8424

DOI - 10.1073/pnas.97.2.783

Subject(s) - peptide , in vitro , drug discovery , computational biology , pathogen , drug development , biology , drug , in vitro toxicology , pharmacology , bioinformatics , biochemistry , immunology

Genome projects are generating large numbers of potential new targets for drug discovery. One challenge is target validation, proving the usefulness of a specific target in an animal model. In this paper, we demonstrate a new approach to validation and assay development. We selected in vitro specific peptide binders to a potential pathogen target. By inducing the expression of a selected peptide in pathogen cells causing a lethal infection in mice, the animals were rescued. Thus, by combining in vitro selection methods for peptide binders with inducible expression in animals, the target's validity was rigorously tested and demonstrated. This approach to validation can be generalized and has the potential to become a valuable tool in the drug discovery process.

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