ABSTRACT
We found that untenone A and mannzamenone A inhibit mammalian DNA polymerases alpha and beta, and human terminal deoxynucleotidyl transferase (TdT). The syntheses of both compounds and the structure-activity relationships of untenone A derivatives are described.
Subject(s)
Cyclopentanes/pharmacology , Formates/pharmacology , Indans/pharmacology , Levulinic Acids/pharmacology , Nucleic Acid Synthesis Inhibitors , Cyclopentanes/chemical synthesis , DNA Nucleotidylexotransferase/antagonists & inhibitors , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Formates/chemical synthesis , Humans , Indans/chemical synthesis , Levulinic Acids/chemical synthesis , Molecular Structure , Structure-Activity RelationshipABSTRACT
[reaction: see text] Construction and characterization of the C-glycosidic moiety of telomerase inhibitor D8646-2-6 (1) are described. This is the first example of the C-glycosylation using electron-poor aromatics, 4-hydroxypyrone, as a glycosyl acceptor. The glycosylation reaction and base-promoted isomerization affords desired beta-C-glycoside in a 61% overall yield.
Subject(s)
Enzyme Inhibitors/chemical synthesis , Glycosides/chemistry , Glycosides/chemical synthesis , Telomerase/antagonists & inhibitors , Enzyme Inhibitors/chemistryABSTRACT
We report that the synthetic peptide Prp106-126 (KTNMKHMAGAAAAGAVVGGLG-COOH) and the reversed peptide Prp126-106 (GLGGVVAGAAAAGAMHKMNTK-COOH) of human prion (hPrp) can express the decarboxylase activity for oxaloacetate in the presence of trifluoroethanol, similar to that of Oxaldie 1 (LAKLLKALAKLLKK-CONH2) reported previously. The degree of the relative activity of Prp106-126 and Prp126-106 to Oxaldie 1 is 0.47 and 0.21, respectively. Based on this experimental result, we applied the informational system method (ISM) developed by Veljkovic et al. to the amino acid sequence of Prp106-126 and Prp126-106 to extract a common factor. The same spectra were obtained, indicating that the same periodicity may be conserved on their sequences, as a necessary factor for expressing the same biological activity, irrespective of the orientation of the primary sequence.
