5453895
Description
Flashcards by Valentina Valenz, updated more than 1 year ago
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Created by Valentina Valenz
almost 8 years ago
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| Question | Answer |
| STRATEGY 1 (3 points to be made) | BINDING BETWEEN DNA BASES - intercalating drugs contain planar aromatic/heteroaromatic ring systems - small enough to fit between holes - once bound inhibits enzyme involved in replication + transcription |
| STRATEGY 1 EXAMPLE 1 | Doxorubicin - naturally occurring antibiotic, anthracydines - intercalates into DNA, is a poison to topoisomerase II, stabilizes complexes, APOPTOSIS - can chelate iron from hydroxyquinone to form iron-DNA complex causing a single strand break - causes cardio toxicity side effect -inhibits DNA helicase |
| STRATEGY 1 EXAMPLE 2 | Ditercalinium -tetracation therefore has ionic interactions with DNA phosphate ester - adds stability to adduct, too many stablised complexes leads to APOPTOSIS |
| STRATEGY 2 (4 points to be made) | BINDING TO THE GROOVES OF DNA - small molecules will react with DNA by binding to the grooves -major groove: when DNA backbone are far apart - minor groove: when DNA backbone are close together - DNA binding occurs mostly at major groove as to avoid backbone |
| STRATEGY 1 EXAMPLE 1 | NEOMYCICN -binding affinity (7.1-8.5 k.cal.mol-1) - groove binding characteristics: cyclohexane rings attached by oxygen atoms |
| STRATEGY 1 EXAMPLE 2 - PARMOMOYCIN (structure) | |
| STRATEGY 3 (4 points ot be made) | ALKYLATING DNA - most potent way to target cancer with natural products - strained three-membered ring "chemical warhead" heterocycles - drugs interact with DNA by forming interstrand crosslinks -highly electrophilic compounds with poor selectivity |
| STRATEGY 3 EXAMPLE 1 | |
| STRATEGY 3 EXAMPLE 2 | DUOCARMYCIN - protonation at heteroatom, activates electrophile so can react with a weak nucleophile - dienone ir protonated reduced electron density in pi system by activating heat - alkylated by N-adenine |
| STRATEGY 4 (1 points to be made) | CLEAVING OF DNA -DNA cutters cleave strands of DNA and prevent enzymes to fix it - DNA radicals appear on the structure + react with oxygen to form peroxy species which irreversibly change the DNA - "enedyiene" systems undergo Bergmann rearrangement to form a diradical |
| STRATEGY 4 (general) | |
| STRATEGY EXAMPLE 1 | |
| STRATEGY EXAMPLE 2 | CALICHEAMICINS - a series of Michael additions followed by the Bergmann rearrangement resulting in a diradical and thus cleaving DNA |
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