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Journals and Conferences
Toxic and mutagenic O6-alkylguanine adducts in DNA are repaired by O6-alkylguanine-DNA alkyltransferases (MGMT) by transfer of the alkyl group to a cysteine residue in the active site. Comparisons in silico of prokaryotes and lower eukaryotes reveal the presence of a group of proteins [alkyltransferase-like (ATL) proteins] showing amino acid sequence… (More)
The human DNA repair protein O6-methylguanine DNA methyltransferase (MGMT) dealkylates mutagenic O6-alkylguanine lesions within DNA in an irreversible reaction which results in inactivation of the protein. MGMT also provides resistance of tumours to alkylating agents used in cancer chemotherapy and its inactivation is therefore of particular clinical… (More)
The human DNA repair protein O-methylguanine DNA methyltransferase (MGMT) dealkylates mutagenic O-alkylguanine lesions within DNA in an irreversible reaction which results in inactivation of the protein. MGMT also provides resistance of tumours to alkylating agents used in cancer chemotherapy and its inactivation is therefore of particular clinical… (More)
The syntheses of novel tricyclic pyrrolo[2,3-d]pyrimidine analogues of O(6)-methylguanine and S(6)-methylthioguanine are described. The crystal structures and pK(a) values of these analogues are reported. In a standard substrate assay with the human repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) only the oxygen-containing analogue displayed… (More)
Incorporation of a bicyclic cytosine analogue, 3-beta-D-(2'-deoxyribofuranosyl)-7,8-dihydropyrido[2,3-d]pyrimidine, into synthetic DNA duplexes results in a greatly enhanced thermal stability (3-4 degrees C per modification) compared to the corresponding unmodified duplex.
O6-alkylguanine DNA alkyltransferase (AGT) is a key target for inhibition during cancer chemotherapy. A large number of O6-modified-guanine analogues have been developed as AGT inhibitors, of which benzyl and (4-bromothenyl) have been used clinically. Since the normal AGT substrate is the alkylated guanine in DNA, the inhibition of AGT by oligonucleotides… (More)
We synthesised a novel membrane-insertable amphiphilic DNA. The amphiphilic DNA had a nine-nucleotide hydrophobic region at one end consisting of octyl phosphotriester linkages. The amphiphilic DNA bound to the lipid membrane by inserting the hydrophobic region; this process was facilitated by the presence of the complementary DNA strand.
Expression of the cafA gene at 71 min on the E. coli chromosome map by use of a high copy number expression vector caused (1) overproduction of the 51 kDa CafA protein, (2) formation of chains of normal cells and shorter anucleate cells, and (3) formation of flexible, tough structures, which we call 'cytoplasmic axial filaments', running throughout the… (More)