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20 Cards in this Set

  • Front
  • Back
Potential Drug Mechanisms
-Drugs that permanently destroy/disable genes
-Drugs that destroy RNA message
-Drugs that protect RNA message
-Drugs that Silence Genes
Two mechanisms of ASODN (Antisense oligodeoxynucleotides)
blocks the DNA translation machinary and form and ODN-RNA complex where the Double-stranded RNA is destroyed by RNase H
ASODN mechanism
-Double-stranded RNA destroyed by RNase H
-Also blocks the translation process
Salutary Properties of AS Drugs
Highly Specific
Universally applicable
Versatile applicability
Verifiable efficacy
Rapid development Pharmacologically Predictive
The first antisense drug for clinical use
Vitravene or Fomivirsen (Novartis)
-treats cytomegalovirus (CMV) retinitis in people with AIDS.
Diferences between antisense drugs and siRNA Drugs
Double-stranded RNA,transported into nucleus
- siRNA is double-stranded
-Requires cytoplasmic processing by RISC
-Ds-siRNA/mRNA destroyed by ribonuclease(versus RNAHase
MicroRNAs
natural antisense oligonucleotides
Size of MicroRNAs
Small RNA molecules comprising 21-23 nucleotides
Varieties of miRNAs
Some 700 identified miRNAs regulate 30% of human genes
methyltransferases
activates Methylation
Methylation
promoters for specific genes prevents the binding of the transcriptome to the promotor, hence inhibiting transcription
histone acetyltransferase
activates Acetylation
prevents DNA compaction, resulting in enhanced readiness for transcription
Acetylation
histone deacetylase
deacetylation
Hydroxymate,benzamide
Drugs that Inhibit Histone Deacetylase
Drugs that Inhibit DNA Methylation
cytidine,5-methylcytidine,
siRNA Drugs
-siRNA is double-stranded
-Requires cytoplasmic processing by RISC (RN
A-induced silencing complex
-Ds-siRNA/mRNA destroyed by ribonuclease
how does actylation and deacetylation controlled?
Acetylation is activated by histone acetyltransferase
and
reversed by histone deacetylase
What is the significance of acetylation?
Acetylation prevents DNA compaction, resulting in enhanced readiness for transcription
What is the significance of acetylation
ctosine Methylation of promoters for specific genes prevents the binding of the transcriptome to the promotor, hence inhibiting transcription