theme 2 examples

Question 1

what is chlorocyclizine

Answer 1

an antihistamine that that targets H1 histamine receptors and acts as an atagonist here

Question 2

what type of receptor is H1

Answer 2

muscarinic

Question 3

how does chlorocyclizine act in hepatitic C viral infection

Answer 3

it binds to the E1 envelope gylcoprotein. This prevents the virus from fusing with the host cell and therefore endocytocis of vral RNA

Question 4

what is the difference betweeen endocytosis and exocytosis

Answer 4

endo - entering
exo - exiting

Question 5

what is a glycoprotein

Answer 5

a protein that has carbohydrates attached

Question 6

was the discovery of chlorocyclizine having activity against HCV a) moleculat target based screening or b) phenotypic screening

Answer 6

phenotypic

Question 7

how was Gluc and cre recombinase used in the screen to assess Hepatitus C viral activity.

Answer 7

Host cells genetically engineered to express CAG promotor upstream of reporter gene - G.luciferase gene
Promotor separated by intervening sequence - prevents generation of luciferase
Intervening sequence flagged by cre recombinase - allows dna sections to be removed

Cre enzyme cuts at cre sites if present = promotor can drive luciferase expression

Cre enzyme encoded in virus = removal of intervening sequence = luciferase expression = luminescence

So if virus interferes with the cell then the cre recombinase enzyme will cut the interfering sequence out leading to luminescence. This is a method of seeing if viral activity is taking place.

Question 8

what screening tool was used to cgaracgterise the formation of VEGFR2 homodimers and ligand binding ar VEGFR2 and how does this work

Answer 8

BRET - bioluminescent energy transfer:
both receptors are tagged with biolumiescent substrates that when in close proximity, the resonant energy transfer leads to biolumiecence energy emission.

Question 9

in people with narcolepsy which neuron are they lacking

Answer 9

orexin neurons

Question 10

what is orexin

Answer 10

plays a key role in wakefull ness. orexin binds to GPCRs to stimulate nueurotransmission and promote wakefullness.

Question 11

what is an orphan receptor

Answer 11

a receptor that we do not know the endogenous ligand for

Question 12

what is the role of CaSR

Answer 12

maintains calcium homeostasis. It inhibits synthesis and relase of parathyroid hormone. PTH stimulates bone resorporbion (bone matrix broken down and calcium stored in bones is released back into blood) and renal calcium reabsorbtion from waste filtred fluid into blood.

Question 13

what drus acts to decrease calcium in the blood

Answer 13

cinacalet

Question 14

does cincalet bind allosterically or orthosterically

Answer 14

allosterically

Question 15

what is allosteric binding

Answer 15

binding to a site that is not the active site

Question 16

how is herpes virus encoded GPCRS used as a drug target

Answer 16

herpes viraus encoded GCRS are proteins that are endoded by viral DNA so when a host cell is infected by a viruses DNA they express the viral GPCR on their surface membrane.
These GPCRs respond to human chemokines that stiumlate cell division. This is how viruses can lead to cancer as they can be uncontrolled cell growth and replication. Drugs that antagonise this receptor will prevent the growth and replication of the cell, preventing spread of the virus and tumor formation

Question 17

describe the structure of a receptor tyrosine kinase

Answer 17

epidermal growth factors are receptors that contain a tyrosine kinase ezyme - receptor activation can activate this enzyme
Tere is an extracellular ninding region and an intracellular tyrosine kinase region
the ectracellular region can contain a dimerisation domain. opening og a dimerisation domain can be agonist led or sponateous

Question 18

give an example of Human epidermal growth factor receptors and their link to disease

Answer 18

HER2 (ErbB2) - linked to breasr cancer

Question 19

does inhibiton of the tyrosine kinase region effect KD

Answer 19

no. This only effects the efficacy. ie Emax
no effect to the binding of the extracellular domaon

Question 20

what is Nintedanib

Answer 20

a multi-targeted tyrosine kinase inhibitor

Question 21

for what interaction is BRET and FRET used for

Answer 21

Protein-protein

Question 22

difference between BRET and FRET

Answer 22

B - biolummienscence - no excitatiry light needed
F - flourescence - excitatort light needed

proximity is the key thing we are measuring in both
close proximity = resonant energy transfer = signal

Question 23

what is rampamycin

Answer 23

immunosurpessant used in transplant

Question 24

what is the MOA of rapamycin

Answer 24

binfs to immunophilin FK506 binding protein = complex that inhibits kinase activarion = dec protain synthesis and cell cycle arrest (ie no cell division)

Question 25

what method was used to assess Ripamycin activity

Answer 25

BRET

Question 26

what is the CRISPR/Cas9 system and how is this used in drug discovery

Answer 26

gene editing tool
CRISPR - repeats of dna - make bacteria immune to attack
introduces mutations into genes to create models of human diseases, it can correct disease causing mutations in cells and assess whether gene editing and removal is a valid approach for therapy

CAS9 - Molecular scissors
recognises the tracRNA region and cuts here

Question 27

what are nanobodoies

Answer 27

nanovodies are singular domaons of antibodies. they are the variable region of the anibody
they contain regions that make them secific to the target: COMPLEMENTARY DETERMINING REGIONS (CDRs)
they can have a HiBit attached to them so when they are bound to the target that has a nanoLucferase present, luminescence is given off and we can see visually that the nanobody is bound to the target

Question 28

what are P2Y12 receptors used for

Answer 28

ADP receptors that mediate platelet aggregation
these receptors are present on platlets. ADP stabalises platelet aggregates. deficiency can lead to excessibe bleeding as there is decreased aggregation of platlets. This is also a target for thrombosis to prevent aggregation

Question 29

what are p2y2 receptors used for

Answer 29

ATP recepotrs used in cancer cell metastasis

Question 30

what is the drug name that targets p2y12 in the management of thrombosis

Answer 30

ticagrelor - allosteric antagonist

Question 31

how does ATP released from Platelets have a role in cancer metastisis

Answer 31

ATP activated P2y2 receptors that stimulates metasitis s

Question 32

how does apyrase work

Answer 32

prevents platelet dependant facilitation of tumour migration (metastasis)