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Investigation of the genetic functions in complex biological systems is a challenging step in recent year. Hence, several valuable and interesting research projects have been developed with novel ideas to find out the unknown functions of genes or proteins. To validate the applicability of their novel ideas, various approaches are built up. To date, the most promising and commonly used approach for discovering the target proteins from biological system using small molecule is well known a forward chemical genetics which is considered to be more convenient than the classical genetics. Although, the forward chemical genetics consists of the three basic components, the target identification is the most challenging step to chemical biology researchers. Hence, the diverse target identification methods have been developed and adopted to disclose the small molecule bound protein. Herein, in this review, we briefly described the first two parts chemical toolbox and screening, and then the target identifications in forward chemical genetics are thoroughly described along with the illustrative real example case study. In the tabular form, the different biological active small molecules which are the successful examples of target identifications are accounted in this research review. [ABSTRACT FROM AUTHOR]

Chemical genetics is a powerful method which utilizes small molecule regulators to reveal the molecular basis of diverse biological processes. However, the current chemical genetic approach sometimes meets a serious bottleneck during the process of target identification. One faces difficulty in conjugating the active compound to an affinity matrix without losing or reducing its activity that leads to laborious structure–activity relationship (SAR) studies. To facilitate this process, we have developed a tagged triazine library containing a built-in linker that provides a straightforward transition from phenotypic screening to target identification. A strategy for constructinig a tagged library and applications with a streamlined target identification and subsequent mechanistic study are discussed in this Account. [ABSTRACT FROM AUTHOR]

The article offers information about chemical genetics, a branch of chemistry that deals with studies on a gene's role by altering the activity of cognate protein, using small molecule inhibitors analogously to the genetic knockout. Chemical genetics is divided into two approaches: the phenotype to genotype which requires no specific gene target from the onset and the forward chemical genetics which substitutes random mutagenesis with a collection of unbiased compounds as protein function regulator.

As most of the available depigmenting agents exhibit only modest activity and some exhibit toxicities that lead to adverse side effects after long-term usage, there remains a need for novel depigmenting agents. Chemical genetic screening was performed on cultured melanocytes to identify novel depigmenting compounds. By screening a tagged-triazine library, we identified four compounds, TGH11, TGD10, TGD39 and TGJ29, as potent pigmentation inhibitors with IC50 values in the range of 10 μM. These newly identified depigmenting compounds were found to function as reversible inhibitors of tyrosinase, the key enzyme involved in melanin synthesis. Tyrosinase was further confirmed as the cellular target of these compounds by affinity chromatography. Kinetic data suggest that all four compounds act as competitive inhibitors of tyrosinase, most likely competing with l-3,4-dihydroxyphenylalanine ( l-DOPA) for binding to the DOPA-binding site of the enzyme. No effect on levels of tyrosinase protein, processing or trafficking was observed upon treatment of melanocytes with these compounds. Cytotoxicity was not observed with these compounds at concentrations up to 20 μM. Our data suggest that TGH11, TGD10, TGD39 and TGJ29 are novel potent tyrosinase inhibitors with potential beneficial effects in the treatment of cutaneous hyperpigmentation. [ABSTRACT FROM AUTHOR]