AT L3 Intercalators

Question 1

2 drugs that target topoisomerase2 (TOP2)

Answer 1

anthracycline and doxorubicin

Question 2

How do drugs target TOP2

Answer 2

trapping an enzyme intermediate termed the COVALENT COMPLEX

Question 3

problem with anthracycline

Answer 3

limited by cardiotox

Question 4

problems with targeting TOP2

Answer 4

formation of secondary malignancies that arise from drug-induced translocations (moniitor foe several years afterwards)

Question 5

New drugs are being developed to target TOP2 how?

Answer 5

catalytic inhibition of TOP2

Question 6

what sort of damage is TOP2 mediates

Answer 6

strand breaks and proteins that are covalently bound to DNA.

Question 7

What mechanisms repair TOP2 damage

Answer 7

ds repair

other pathways that are specific for removal of protein-DNA adducts

Question 8

compounds targeting topoisomerase mode of action

Answer 8

aromatic rings intercalate, extends the duplex.
Act by trapping intermediate complex and freeze it.

(different from other drugs that cause damage to DNA - this sticks for DNA)

Question 9

the drugs structure more or less is

Answer 9

planar, 3-5 aromatic rings, stack on top of base pairs - distortion.
Sugar moety binds to the groove increasing binding strength

Question 10

Neighbour exclusion rule

Answer 10

ypu can only get one molecule between every 4 base pairs as they push base pairs appart

Question 11

Doxorubicin and SN-38 mode of action

Answer 11

stabilise TOP2 or TOP1 respectively.

Producing a cleavable complex.

Question 12

PLuramycin mode of action

Answer 12

binds peripherally at TATA binding protein which gets immobilised onto the DNA

Question 13

What sequence repeats does telomerase target?

Answer 13

TTAGGG

Question 14

DNA sequences that can form quadreplexes invilve….

Answer 14

telomeres and promoters that contain a polypurine-rich strand

Question 15

equilibrium between double stranded DNA and G quadraplex os dependant on

Answer 15

helicases (unwind quadraplex)

Question 16

mode of action of G-quadraplex interactive drugs…

Answer 16

inhibit helicases
or
facilitate formation of new G quadraplexes
or
sequester newly formed G quads

Question 17

what is a g quad

Answer 17

guanine forms stable structures ~(with correct salt conc). They stack together.