RECEPTORS Flashcards
Describe 1st gen biopharmaceutics
Copies of proteins are transfected into expression systems like E.coli
Describe 2nd gen protein biopharmaceutics
Engineer to alter the protein to improve its properties
Describe the structure of an antibody
- Light chain made up of hypervariable region, variable region and the complement fixation region
- Heavy chain made up of FC region
What is trastuzumab?
A humanized monoclonal HER targetting antibody that gets replaced with FC region of an antibody
Describe 3 monoclonal antibody drugs
- Bevasizumab = targets VEGF
- Cetuximab = targets EGFR
- Gleevec = inhibits intracellular tyrosine phosphorylation
What is checkpoint therapy?
Using checkpoint antibodies to prevent tumour cells/TME from using checkpoints to protect themselves from immune system attacks
How is checkpoint therapy used in cancer treatment?
In melanoma targetting CTLA4 and PD1
How many receptors are there in the nuclear receptor family and give an example?
- 48 soluble receptors
- ERA
Give examples for nuclear receptor ligands
- Steroids and retinoic acid (vitamin A)
Describe the core domain of nuclear receptors
- Highly conserved
- Has 2 zinc fingers that bind HRE sequence on DNA
Describe the structure of kinase linked receptors and give and example
- Made up of 1000 amino acids
- Has an extracellular ligand binding domain, transmembrane domain and intracellular domain
E.g. RTK and cytokine receptors
What is the orthosteric site?
Where ligand binds
What is the allosteric site?
Where the drug (inhibitor) binds
What is the venus fly trap?
When the ligand binds and the protein closes around it
Describe the abundance of GPCRs in the human genome
- Makes up 4% of the entire human genome
- 500 of them are for smell and taste
What are GPCRs mediated by and give examples of effectors?
- Mediated by heterotrimeric G proteins (alpha/beta/gamma subunits)
- E.g. AC, PLC
Give 3 examples of GPCR pathways
- B2 adrenergic > GaS > increase AC, CAMP
- M2 muscarinic > Gai > inhibits AC
- P2Y2 purinergic > GaQ > increase PLC, IP3, DAG
Describe the 3 ways ion channels are gated
- Ligand-gated = NTs
- Voltage-gated = change in membrane potential
- Stretch-gated = change in pressure of plasma membrane
Describe how ion channels are excited/inhibited
Excited by cations coming in = depolarisation (membrane potential more positive)
Inhibited by cations going out = hyperpolarisation (membrane potential negative)
Give 3 examples of ligand-gated ion channel
- Nicotinic acetylcholine receptor
- GABAA
- NMDA/AMPA (glutamate)
Describe a neurotoxin that inhibits the nicotinic acetylcholine receptor
Alphabungra toxin
Describe the structure of nicotinic acetylcholine receptor
Pentameric with 2 acetylcholine binding sites
What are the different forms of GPCRs?
Homodimers and heterodimers or heterodimers between GPCR classes
What are the most common nAChr subunits in the brain?
- Heterooligomeric receptor made up of 4 alpha and 2 beta subunits
- Oligomeric receptor made up of 7 alpha subunits
