LEUSCH NEW

siRNA
True
1. They have a length of approximately 21-23 nucleotides
2. They are double stranded
3. they inhibit gene expression by degrading homologous mRNA
si RNA
False:
1. they inhibit replication by annealing to homologous DNA sequences
2. they work by a posttranslational gene splicing mechanism
3. they cleave transcription factors, thereby inhibiting gene expression
Which statements about chemical (compositional) and regulatory differences between natural drugs and herbal remedies (botanical dietary supplements) are true?
? Herbal remedies are mixture compounds
? Herbal remidies don’t require FDA approval
? Natural product drugs are usually given single agents
Give reasons for potential problems associated with toxicity and/or lack of activity
? Contamination with pesticides/herbicides/heavy metals
? Use of incorrect part of plant
? Active component not present or has inconsistent amounts
? Active compound produced by a microorganism
? Interactions with other botanicals or medications (not rigorously tested)
Which of the following are NOT marine natural products
? TAXOL
? ERYTROMYCIN
? CYCLOSPORIN A
True statements
? Taxol is diterpenederived
? An isoprene unit consists of five carbons
? Cocaine is an alkaloid
? Peptides and polypeptides are commonly synthesized by bacteria
Which two statements are true about the drugs GLEEVEC, TYKERB, and NEXAVAR
-They inhibit kinases
? They inhibit intracellular signaling to transcription factors
Associate the herbal remedies with the claims/potential applications
Antidepressant=St. john’s wort
? Antiseptic, antiviral, immunostimulant=Echinacea
? Antiinflammatory, antiasthmatic, treatment for dementia=Ginko
? Stamina, stress resistance, healing, against age associated degeneration=Ginsing
Describe the mech of action (MOA) of histone deacetylase (HDAC) inhibitors and explain why they may be useful for anticancer therapy.
By preventing the deacetylation of histone, HDAC inhibitors r educe electrostatic interactions between negatively charged DNA and positively charged lysine residues of histones, thereby loosening the chromatin and activate gene expression
? Reactivation of tumor suppressor genes or regulators/inhibitors of the cell cycle may have anticancer effects
Describe the MOA of indirect antioxidants via transcription factor Nrf2 and give one example of a phytochemical/vegetable with that activity.
They induce the nuclear translocation of Nrf2. Nrf2 then binds a DNA sequence in the promoter region of the genes encoding antioxidant and detoxification enzymes, leading to their gene expression and subsequently increased antioxidant status in the cell.
Assume you find a sponge during a collection trip with the Luesch group in the
Florida Keys and back at UF you isolate an active compound that structurally appears to be a peptidepolyketide hybrid. Six months later you recollect the sponge from the same dive site, however, you don’t find the same compound again. Give 2 reasons why.
? Seasonal variation in metabolite production
? Compound may be produced by a symbiotic organism/bacterium that wasn’t present six months ago
. Assume you have discovered an anticancer compound w/ toxic SEs on normal cells. Provide strategies to increase the therapeutic window of the agent.
? Structural modification may lead to improved selectivity
? Conjugation to an antibody could assure preferential delivery to the tumor target site
Give reasons why protease inhibitors may be useful for cancer therapy
? Protease inhibitors stabilize certain proteins by preventing or retarding their degradation. Therefor they may be able to stabilize tumor suppressors and/or endogenous cell cycle inhibitors and/or cytoplasmic inhibitors of cancer associated transcription factors
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