Analogues of Nucleic Acid Components: Mechanisms of Action by P. Roy-Burman Ph. D. (auth.), P. Roy-Burman Ph. D. (eds.)

By P. Roy-Burman Ph. D. (auth.), P. Roy-Burman Ph. D. (eds.)

The purpose for the layout of structural analogues of a regular metabolite is that such compounds could intervene within the usage or functionality of the metabolite. A compound that's potent during this admire will be referred to as an antimetabolite. to achieve success in chemotherapy of bacterial, viral, or tumor development, an antimetabolite may still adversely have an effect on a few important metabolic reactions within the parasite or parasitic tissue with out heavily endangering the host tissue. If a metabolic strategy of the offending progress isn't like that of the host, it's most probably that the metabolism or job of a compound, structurally on the topic of a metabolite enthusiastic about that procedure, may also be varied in those cells. Such changes are necessary for devising powerful medicines with selective activities. Sulfanilamide, a structural analogue of para­ aminobenzoic acid, interferes with the usage of this metabolite within the synthesis of folic acid, a vital issue for progress. micro organism synthesize their very own folic acid and are incapable of using exogenously to be had folic acid. besides the fact that, the placement is strictly contrary within the animal host. that's, animal tissues can't synthesize folic acid and are totally based upon exogenous assets. those transformations in metabolism make attainable using sulfanilamide as a selective inhibitor of progress. different antibacterial or antiparasitic medications, corresponding to penicillin (BURCHALL, FERONE and HITCHINGS, 1965) and inhibitors of dihydrofolate reductase (HITCHINGS and BURCHALL, 1965; HITCHINGS, 1964; BURCHALL and HITCHINGS, 1965) have analogous fascinating selective toxicity effects.

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22). The first step is catalyzed by nucleoside phosphorylases and the equillibrium of the reactions favors degradation. The specificity of nucleoside phosphorylases is not well documented. However, some nucleoside phosphorylases which act on uracil and thymine do not act on purines. The second step is catalyzed by nucleosidase kinase, and phosphate is donated by a ribo- or deoxyribonucleoside triphosphate. Several pyrimidine nucleoside kinases have been isolated which show specificity for nucleosides.

The substitution of one of the G residues by aza-G results in a lower template activity, and when both of the residues are replaced by aza-G the recognition by the triplet is highly diminished. A possibility has been considered that the growing polypeptide chains may terminate prematurely when the anomalous aza-GpUpaza-G sequence in the mRNA molecule is reached. This gains support from the observations that during the protein synthesis in the ribosomal system from aza-G-treated B. cereus cells most of the amino acids are incorporated into unfinished polypeptide chains which remain bound to the ribosomal particles and are not released into the supernatant fraction (GRUNBERGER, HOLY and SORM, 1968).

Coli have been observed to be inhibited by ara-ADP (LUCAS-LENARD and COHEN, 1966). 9-fJ-D-X ylofuranosyladenine (Xylosyladenine) l","H2 N)y~ lNJ-N ROC;R~O, I ~ OR Xylosyladenine NH2 t~) HO~ OR OR Adenosine 9-P-D-Xylofuranosyladenine (xylosyladenine or xyl-A) is an adenosine analogue in which the hydroxyl group on carbon 3 of the sugar is transposed. The nucleoside analogue was synthesized by CHANG and LYTHGOE (1950) and has shown effectiveness in prolonging the survival time of. mice bearing TA3 or Ehrlich ascites tumors (ELLIS and LEPAGE, 1965).

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