Drug, drugs chemical genetics

Effective P13K/PKB pathway interruption has also been reported with a series of compoimds whose mechanism of action is still unknown. The three examples reviewed in this section also illustrate the potential application and challenges that chemical genetics may face in this area of drug discovery. 

To date, complex proteins with biological activity (6), for use in X-ray crystal structure analysis (7) and ELISA systems (8), and for the development of animal drugs (9) have successfully been produced by using this system. Therefore, the Kaiko-baculovirus protein production system has broad applicability across the field of reverse chemical genetics for the analysis of protein function on the basis of interactions with chemical compounds. 

Physical and chemical genetic techniques have been used to enhance the permeability of yeast membranes. Permeabilizing agents, such as polymyxin B sulfate and polymyxin B nonapeptide, have been used to physically disrupt the integrity of yeast membranes (14). However, use of such chemical agents in drug screening is not ideal, because of the toxicity induced by polymyxin B treatment. 

Since the discovery of this phenomenon with isoniazid over 40 years ago, nearly a dozen related drugs and chemicals have been found to be similarly influenced by genetic variation in this acetylase enzyme. Therefore, the likelihood of a slow acetylator encountering such a chemical/drug has increased. DNA amplification assay techniques of samples obtained from leukocytes, single hair roots, buccal epithelia, or other tissue have been developed that can be used to predict the acetylation phenotype of an individual. The availability of such information could, theoretically, be used to assess workers at high risk for toxicity (e.g., chemical workers exposed to arylamines normally inactivated by acetylation). 

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