Down-regulation of H tau 40 protein expression by minor groove binders.
The DNA minor groove binders SN6999, SN6570, and SN6113, structurally related to netropsin and distamycin, were investigated for sequence-specific interactions with the 154 base pair cDNA fragment of the human tau 40 protein, involved in pathology of Alzheimer's disease. Footprinting results indicated that both the former compounds displayed a pronounced AT-preference, while the latter SN-derivative bound to DNA in a non-sequence specific manner. The influence of these ligands on the protein synthesis was analysed using monoclonal antibodies against h tau protein. Both sequence specific binders markedly impeded protein synthesis. The non-specific binder, however, did not affect protein biosynthesis.
Kittler
L
L
Institute of Molecular Biotechnology, Department of Single-Cell and Single Molecule Techniques, Jena, Germany.
Wollweber
L
L
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D018983:DNA Footprinting; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism*; D003864:Depression, Chemical; D004926:Escherichia coli; D005786:Gene Expression Regulation / Q000187:drug effects*; D005796:Genes / Q000187:drug effects*; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000737:chemistry / Q000494:pharmacology*; D011806:Quinolinium Compounds / Q000737:chemistry / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D016875:tau Proteins
D018076:DNA, Complementary; D008565:Membrane Proteins; D009842:Oligopeptides; D011725:Pyridines; D011726:Pyridinium Compounds; D011806:Quinolinium Compounds; D011993:Recombinant Fusion Proteins; C404786:SN 6570; C079604:SN 6113; C062476:SN 6999; C054369:MAPT protein, human; D016875:tau Proteins