PBD - Antitumour Abx

Question 1

PBD stands for…

Answer 1

Pyrrolobenzodiazepine (PBD)

Question 2

SJG - 136 binds to the ____ groove of DNA to the N2 positions of ____ on opposite strands of DNA

Answer 2

Minor

Guanines

Question 3

What moiety on PBDs e.g. SJG-136 binds to DNA?

Answer 3

Imine moiety (N10-C11 and N10’-C11’)

Question 4

High stability of _____ crosslinks formed by SJG-136 inhibit __ _______ from reading through the drug binding site and so transcription is halted. ____ cross link duplex adducts can also be formed.

Answer 4

Interstrand
RNA polymerase
Intrastrand

Question 5

SJG-136 - DNA adducts are ___ resistant to repair than those of other DNA interacting agents

Answer 5

MORE

Question 6

What species of bacteria produces PBD monomers?

Answer 6

Streptomyces species of bacteria

Question 7

What nitrogen do PBDs bind to?

Answer 7

Exocyclic amino group of guanine base of DNA

Question 8

The cardiotoxicity of anthramycin and sibiromycin is thought to be due to presence of __ _____.

Answer 8

C9 oxygen

Question 9

Crosslinking of DNA prevents process that require the ____ of DNA.

Answer 9

Seperation

Question 10

Repair of cross-linked DNA involves i___ and ‘u_____’ of cross link by structure specific e_____ including XPF-ERCC1 and processing by h______ r______.

Answer 10

Incision
Unhooking
Endonucleases
Homologous recombination

Question 11

SJG-136 and ____ can be used in combination as _____ suppresses transcription of DNA cross link repair protein ______ and inhibited SJG-136 induced ______ transcription when given in combination

Answer 11

Fludarabine
ERCC1
ERCC1