GTP Cyclohydrolase Functions in Fish Color Formation / 中国生物化学与分子生物学报

Guanosine triphosphate cyclohydrolase (GTP cyclohydrolase,Gch) is a protease with a GTP- cyclohydro domain, which is widely found in vertebrates and invertebrates.Mammals and birds only have Gch 1.In teleost and amphibian, other two paralogs (Gch2 and Gch3) also exists besides Gchl, which also displayed functional differences.Gch is a rate-limiting enzyme that ultimately synthesized the tetrahydrobiopterin (BH4) using guanosine triphosphate as a substrate.BH4 is an essential coenzyme of aromatic amino acid hydroxylase and contributes to the synthesis of various hormones and neurotransmitters.The Gch is an initial step in the catalysis of various pterin biosynthesis and plays important roles in a series of physiological and pathological processes, such as skin pigmentation, ocular pigmentation, methotrexate, folic acid, and tetrahydrobiopterin.The physiological function of Gch is inextricably linked to the biosynthesis of BH4.As the only rate-limiting enzyme in BH4 biosynthesis, the activity of Gch is a useful indicator for the development of neurons and pigment cells.Besides, it is also an important marker of pigment synthesis and neurotransmitter biosynthesis.Nowadays, the functions of Geh in pathogenesis of tumor and cardiovascular diseases have been widely concerned, while the researches on the pigmentation and color formation are mainly concentrated in insects, and rarely in teleost.Therefore, this article summarized the characteristics of Gch genes, protein and the functions of Gch in fish coloration, which has important guiding significance for further illustration the mechanism of Gch in teleost pigmentation and fish color genetic improvements.

In-silico ADME and toxcity studies of some novel indole derivatives.

Drug design is a process which begins with a compound that displays an interesting biological profile and ends with optimizing both the activity profile for the molecule. The process is initiated when the chemist conceives a hypothesis which relates the chemical features of the molecule (or series of molecules) to the biological activity. Study of Quantitative structural activity relationships (QSAR) is an important aspect of computational chemistry for optimizing the structural features to obtain better activity. Present research work focuses on in-silico drug design studies of novel indole derivatives containing pteridine and benzimidazole moieties. These studies include QSAR (Quantitative structure activity relationship) and QSTR (Quantitative Structure Toxicity Relationship) and are carried out using different software’s namely DS Viewer Pro suite, Accord for Excel (v6.1) and TOPKAT (v6.2). All the software’s were obtained from Accelrys Discovery studio. In-silico pharmacokinetic studies implied that these derivatives had no CYP4502D6 inhibitions, no BBB penetration and good oral absorptions. QSTR (Quantitative Structure Toxicity Relationship) studies by using TOPKAT (v6.1) in various computational animal models showed high LD50 values and the compounds are found to be noncarcenogenic.