Poly polymerase types

Iq41-q42 47.41 PARP1 Poly (ADP-ribose) polymerase 1 173870 Xeroderma pigmentosum, Fanconi anemia, diabetes type I... 

An identical approach was used by Branca et al. [16] at Merck and led to the identifcationofanovel inhibitor of poly(ADP-ribose) polymerase-1 (PARPl). The 2D descriptors were similar to the CATS all the two-point pharmacophores in each molecule were derived from all possible atom pairs and described in terms of atom types, number of Jt electrons, number of heavy atoms attached, and number of covalent bonds separating the two atoms along the shortest path. Known PARPl inhibitors were collected from patents, publications, and publicly available databases and used to train a support vector machine (SVM) classifier. A SVM constructs the plane that best separates active and inactive compounds in the multidimensional space defined by the molecular descriptors. The results of the SVM were used to classify the compounds in the Merck collection and those predicted to be active were screened. One compound was particularly potent and was chosen as the starting point for a structure-activity relationship (SAR) exploration of this chemical class. Docking studies on the PARPl crystal structure were used to guide the synthetic efforts. 

In eukaryotic cells, DNA damage may induce a several thousand fold stimulation of poly(ADP-ribose) metabolism. A few restrictions and rules apply yeast does not express such a response, and in all other eukaryotes tested so far, the most effective types of DNA damages are those that are substrates for the DNA base excision repair pathway. By far the largest amount of ADP-ribose is processed throi the catalytic domains of two nuclear enzymes poly(ADP-ribose)polymerase-l, (PARP-1), and its catabolic counterpart, poly(ADP-ribose)glycohydrolase (PARC). Other members of the growing PARP family may contribute to this metabolism, albeit to a much lesser extent and with mechanisms that await further elucidation (for reviews see refs. 1,2). 

Anderson MG, Scoggin KE, Simbulan-Rosenthal CM et al. Identification of poly(ADP-ribose) polymerase as a transcriptional coactivator of the human T-cell leukemia virus type 1 Tax protein, j Virol 2000 74(5) 2l69-2177. 

Poly (adenosine 5 -diphosphate ribose) polymerase-1 (PARP-1) [also known as poly (ADP-ribose) synthetase, PARS E.C. 2.4.2.30] is a chromatin-bound enzyme, which is abundantly present in the nuclei of numerous cell types. Single strand breaks in DNA trigger the aaivation of PARP-1, which transfers ADP-ribose moieties from nicotinamide adenine dinucleotide (NAD ) to various nuclear proteins including histones and PARP (automodification domain) itself. This reaaion leads to the generation of nicotinamide, which is an inhibitor (negative feedback) of PARP-1 aaivity. Continuous or excessive activation of PARP-1 (and perhaps other, less well charaaerized members of the PARP enzyme family) produces extended... 

Kroger H, Miesei R, Dietrich A et al. Synergistic effects of thalidomide and poly (ADP-ribose) polymerase inhibition on type II collagen-induced arthritis in mice. Inflammation 1996 20 203-15. 

Kraak M, Smits THM, Kessler B, Witholt B (1997) Polymerase Cl levels and poly(R-3-hydroxyalkanoate) synthesis in wild-type and recombinant Pseudomonas strains. J Bacteriol 179 4985-4991... 

Inhibitors of poly(ADP-ribose) polymerase prevent differentiation in other cells [6, 7]. The previous reports showing that benzamide was an inducer of FEL differentiation suggested that poly(ADP-ribose) polymerase might have a different type of role in Friend cells. However, our results show that Friend cell differentiation is not exceptional and that common mechanisms may be involved in differentiation of diverse cell types. 

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