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Chemical genetics is defined as a genetics study using chemical tools, which has grown into a major wing of chemical biology and a standard tool of many researchers. A survey of contemporary research in chemical genetics is provided with a special emphasis on the techniques and methods in use.

Peptide fragmentation and activity mapping of human lysozyme was carried out in order to define the structural and sequence requirements for anti-HIV activity. The findings suggest that the effects of HL9 on signaling pathways involved in survival, stress, TGF(beta), p53, NF(kappa)B, protein kinase C and hedgehog signaling may reflect changes in host cells that affect susceptibility to infection.

Research has been conducted on the optically active regioisomers. The complete synthesis of all possible IP (sub)3 and IP (sub)4 optically active regioisomers has been carried out via the use of CRL-catalyzed enzymatic resolution and benzoyl migration strategy and the details are discussed.

A tagged triazine library having a built-in linker that provides a straight-forward transition from phenotypic screening to target identification is discussed. The successful target identification has helped to make a breakthrough in showing the mechanism for the observed phenotype.

A mitochondria-targeted rosamine library in C2C12 myogenesis was applied to identify the compound that regulates the muscle differentiation during the remarkable changes undergone by mitochondria. The findings from the study provide insight into the potential application of fluorescent small molecules in the discovery of a bioactive probe that induces a specific cellular response.

The first BODIPY library (BD) is prepared via a Knoevenagel-type condensation reaction and a highly selective glucagon sensor (Glucagon Yellow (BD-105)) is discovered by fluorescence image-based screening method. The results have shown the application of Glucagon Yellow as a glucagon imaging agent in live cells and tissues.

The molecular mechanism of the metal-induced A[beta] oligomerization is investigated with extensive metal ion titration NMR experiments. The transition-metal ions selectively affect the N-terminal region and facilitate intermolecular interactions between the hydrophobic residues.

The first rosamine library is developed by using solidphase chemistry as a potential fluorescent sensor set. The potential of H22 as a glutathione fluorescent probe for monitoring cellular glutathione levels is described.

A synthesis of a combinatorial benzimidazolium dye library is reported and the discovery of the first turn-on fluorescent GTP sensor is reported. On the basis of this unprecedented high selectivity of G49 to GTP and its visual green fluorescence increase, it is proposed to rename this compound GTP Green.

The power of a tagged library approach for efficient forward chemical genetics is demonstrated, by expediting the connection of a hit compound to the affinity matrix by incorporating a linker directly to the library compounds before phenotypic screening. The study also elucidates the first novel small-molecule inhibitors for several ribosomal accessory proteins or their complex as their target.

Styryl dyes are a class of fluorescent, lipophilic cations that are used as mitochondrial labeling agents and membrane voltage-sensitive probes of cellular structure and function. Combinatorial chemistry has grown to be one of the most powerful tools in new drugs and materials discovery, and the combinatorial approach for organelle-targeted fluorescent dyes further demonstrates its prowess.

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]

Examines the synthesis and biological characterization of the ceramide library. Role of fatty acids and metabolites on cellular transduction; Regulation of hormones; Use of representative scheme for natural ceramide.

The diversity-oriented fluorescence library approach (DOFLA) has emerged and found applications in various fields to meet the acute demands for novel fluorescence sensors. The power of this approach has been demonstrated with the impressive discoveries of novel sensors for polymers such as DNA and heparin or for small molecules such as GTP and glutathione ( J. Am. Chem. Soc.2003, 125, 1130− 1131; J. Am. Chem. Soc.2006, 128, 10380− 10381; J. Am. Chem. Soc.2007, 129, 4510− 4511; Chem. Commun.[Online early access]. DOI: 10.1039/b717058k. Published online Dec 11, 2008. http://www.rsc.org/publishing/journals/CC/article.asp?doi=b717058k). Herein we report the application of this approach on quinaldinium fluorescent dye library synthesis on solid support and novel chymotrypsin sensor discovery. The new sensors are not only selective to chymotrypsin over other proteins but also only to the active conformation of chymotrypsin. [ABSTRACT FROM AUTHOR]

A fluorescent dye library approach for the development of a bioanalyte sensor was sought. The screening of a rosamine dye library against diverse macromolecules led to the discovery of a highly sensitive human serum albumin binder, G13, with ∼36-fold fluorescence intensity change. G13showed a highly selective response to HSA over other macromolecules including albumins from other species. The potential use of G13for the detection of HSA in biofluids is described. [ABSTRACT FROM AUTHOR]

By a systematic ionic effect study in colorimetric dye arrays, we effectively suppressed the anion effect using the proper buffer condition and configured a universal cation sensor system. This result cast a warning for careful validation for other anion sensing systems in aqueous solution. [ABSTRACT FROM AUTHOR]

The combinatorial fluorescent dapoxyl dye library was prepared by both solution- and solid-phase synthesis, generating 80 unique dapoxyl derivatives. A fluorescence-based screening toward human serum albumin (HSA) found one highly sensitive HSA binder ( A41-S) with over 55-fold intensity change. Displacement assay showed the selective binding of A41-Sto the site I of HSA, addressing its potential to be a highly selective and sensitive HSA probe. [ABSTRACT FROM AUTHOR]

Two 60+-membered libraries of α-galactosylceramides have been prepared by reactions between activated ester resins and two core, fully deprotected galactosylated sphingoid bases. The libraries were evaluated for their ability to stimulate CD1d-restricted NKT cells, using in vitro stimulation of a murine NKT cell hybridoma line and for their ability to induce the expansion of NKT cells from peripheral blood mononuclear cells (PBMC) of a normal human subject. Our results showed that many compounds constructed on a C18-phytosphingosine base had significant stimulatory activity in both assays. Because no product purification was required, this approach is particularly attractive as a method for rapid synthesis of large libraries of potential immunomodulatory glycosylceramides. [ABSTRACT FROM AUTHOR]

The article focuses on the use of small molecule fluorophores in detecting cell-state switching in high-throughput screening. It discusses the treatment of the myoblasts and myotubes with a dilution of original compounds that was achieved by serial dilutions, and usage of E26 in cell-based screening for muscle differentiation inhibitors. Results suggest E26 can be used in cell-based screening for myogenesis which can be achieved by binding to a certain protein in a myotube state.

Focuses on a novel microtubule destabilizing entity from orthogonal synthesis of Triazine library and Zebrafish embryo screening. Contribution of microtubule functionality in the design of anticancer drugs; Induction of similar morphological changes; Development of straight forward solid phase synthetic pathway.