Nucleic Acids II Flashcards
Cisplatin
Base alkylating agent. Nucleophilic groups are reactive to alkylating agents.
Caused by enviro exposures like benzene and its derivatives in coal and cigarette smoke.
Rxn of alkylating agents forms large covalent adducts to DNA not easily repaired.
Cross-links DNA—> interferes w/ replication.
Actinomycin
Intercalates into DNA (inserts a ring structure that stacks w/ DNA bases), alters double-helical structure. Interferes w/ replication and transcription.
Etoposide and camptothecin
Blcoks replication by inercalation. Target topoisomerase that relax supercoiling (b/c they are nec. to prevent supercoiling).
Which parts of dogma are drug non-specific vs. specific?
Non-specific: DNA, trx, translation
Drug specific: protein, polypeptides, can form diverse structures.
How do nucleoside analogues get into DNA?
Intercalating agents: get in middle, interfere w/ DNA synthesis
Stop topoisomerase fx: they relieve supercoiling
Covalently bind base pairs (can’t be unzipped)
Synthesis of precursor (dNTP)
More specific nucleosides used against retroviruses
Less specific: as chemo.
Where does polymerization occur?
Happens at phospho-diester bond b/w 5’ end of one nucleotide and 3’ OH of another.
Enzymes that polymerize add nucleotides from 5’ to 3’
DNA vs. RNA
DNA has no 2’ OH group. So it’s more STABLE and less prone to hydrolyzation by nucleophilic attack at the 2’ location.
RNA is hydroxylated. Binds uracil not thymine. Usually SINGLE stranded. Hair pin loops. Important for translation to protein (basically can make more complicated structures).
3 classes of RNA
- ) Structural: tRNA, rRNA, snRNA, snoRNA. Help for machinery that translates mRNA into proteins. and splicing.
- ) Regulatory: miRNA, siRNA (down-regulate gene expression)
- ) Information-containing: mRNA (translated to proteins. Translate DNA to RNA to protein).
Puromycin
Mimics amino-acyl tRNA to terminate translation.
Nucleotide analogue that mimics the tRNA acceptor region. Allows peptide transfer and termination of translation.
Binds in RIBOSOME during TRANSLATION, causes termination.
Adenine methylation
In bacteria it can help differentiate older from newly synthesized strands.