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Termination inhibitors

Sanger, F., Nicklen, S. and Coulson, A.R. (1977) DNA sequencing with chain terminating inhibitors. Proceedings of the National Academy of Sciences USA 88, 2815-2819. [Pg.87]

Romies, B. W. Wu, and L. Musick, Crystal-structure based design and synthesis of novel c-terminal inhibitors of HIV protease, J. Med Chem. 37 2274 (1994). [Pg.296]

One of the motive powers for the design of host molecules for nucleotides is their potential utility in chemotherapy. A number of nucleotide analogues exhibit antiviral activity in vitro [73] for example, 2, 3 -dideoxynucleosides are potent chain-terminating inhibitors of HIV reverse transcripase [74]. However, charged and hydrophilic as they are, they can hardly penetrate across cell... [Pg.116]

Before the sequencing begins it is necessary to prepare a short primer that is complementary to a sequence at one end of the DNA strand to be sequenced. This may be prepared enzymatically,622 623 or by non-enzymatic synthesis. The short primer is annealed to the end of the DNA and the resulting molecule is incubated with a DNA polymerase and a mixture of the four mononucleotide triphosphates, one of which is radio-labeled in this position. Four reaction mixtures are prepared. Each mixture contains all four nucleoside triphosphates and also one of four different chain-terminating inhibitors, the most popular of which are the 2, 3 -dideoxyribonucleoside triphosphates ... [Pg.262]

Figure 27-13 Proposed mechanism and transition state structure for the synthetic nucleotidyltransfer activity of DNA polymerase 3 (and other DNA polymerases). The chain-terminating inhibitor dideoxy CTP is reacting with the 3 -OH group of a growing polynucleotide primer chain. This -OH group (as -0 ) makes an in-line nucleophilic attack on Pa of the dideoxy-CTP. Notice the two metal ions, which interact with the phospho groups and which are held by three aspartate side chains. Two of the latter, Asp 190 and Asp 256, are present in similar positions in all of the polymerases. The active centers for the hydrolytic 3 -5 and 5 -3 exonuclease activities of some of the polymerases also appear to involve two-metal catalysis and in-line displacement. See Sawaya et al.27i... Figure 27-13 Proposed mechanism and transition state structure for the synthetic nucleotidyltransfer activity of DNA polymerase 3 (and other DNA polymerases). The chain-terminating inhibitor dideoxy CTP is reacting with the 3 -OH group of a growing polynucleotide primer chain. This -OH group (as -0 ) makes an in-line nucleophilic attack on Pa of the dideoxy-CTP. Notice the two metal ions, which interact with the phospho groups and which are held by three aspartate side chains. Two of the latter, Asp 190 and Asp 256, are present in similar positions in all of the polymerases. The active centers for the hydrolytic 3 -5 and 5 -3 exonuclease activities of some of the polymerases also appear to involve two-metal catalysis and in-line displacement. See Sawaya et al.27i...
Various substances can reduce the rate at which a monomer is converted to polymer. Inhibitors completely suppress polymerizations whereas retarders only reduce the rate. The former deactivate very readily the primary radicals so that growth of polymer chains cannot begin the latter deactivate growing polymer radicals so causing premature termination. Inhibitors are commonly used to stabilize monomers during storage. Many nitro compounds and quinones act as inhibitors and retarders. [Pg.1344]

DNA sequencing with chain terminating inhibitors (Sanger et al., 1977)... [Pg.72]

An alternative to the ddNTP s (as chain terminators) are the arabinonucleoside triphosphates. Arabinose is a stereoisomer of ribose in which the 3 -hydroxyl group is trans with respect to the 2 -hydroxyl group. Such arabinosyl-(ara) nucleotides act as chainterminating inhibitors of E. coli DNA polymerase I in a manner comparable to ddT. The structures of the chain-terminating inhibitors are shown in Figure 3.1. and the principle of the method in Figure 3.2. [Pg.73]

Fig. 3.1. Structures of chain-terminating inhibitors (a) Dideoxynucleoside-5 -triphosphate (b) Arabinonucleoside-5 -triphosphate. Fig. 3.1. Structures of chain-terminating inhibitors (a) Dideoxynucleoside-5 -triphosphate (b) Arabinonucleoside-5 -triphosphate.
F. Sanger, S. Nicklen, and A.R. Coulson. 1977. DNA sequencing with chain-terminating inhibitors Proc. Natl. Acad. Sci. U.S.A. 74 5463-5467. (PubMedl... [Pg.276]

Macromolecular Sites of Activity for the Trichothecenes. All the trichothecenes tested act, in eukaryotic systems, at the site of the 60s ribosome subunit and specifically inhibit peptidyl transferase. However, the trichothecenes are divided into two specific classes relative to this activity and are either initation inhibitors or elongation and/or termination inhibitors. The initiation inhibitors ares 15-acetoxyscirpen-diol 4-acetylnivalenol diacetoxyscirpenol HT-2 toxin nivalenol T-2 toxin scirpentriol verrucarin A (4-0, 11b). [Pg.69]

The elongation and/or termination inhibitors are crotocin crotocal trichodermin trichodermol trichothecin trichothecolone verrucarol (40, 11b). [Pg.69]


See other pages where Termination inhibitors is mentioned: [Pg.77]    [Pg.262]    [Pg.910]    [Pg.914]    [Pg.266]    [Pg.279]    [Pg.4]    [Pg.16]    [Pg.293]    [Pg.486]    [Pg.1812]    [Pg.262]    [Pg.152]   
See also in sourсe #XX -- [ Pg.266 ]




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