BIOC0006: THERAPEUTIC PROTEINS
What are conformational diseases?
caused by misfolded protein aggregates
What kind of diseases are most common?
polygenic
Why are most diseases polygenic?
bc they involve complex pathways
Which pathway is implicated in many diseases?
MAPK
What alterations in MAPK can cause disease?
mutations in BRAF bc its an oncogene
What is Parkinson's caused by?
mutations in alpha synuclein which has tendency to form fibrils
What do synuclein fibrils form?
aggregates known as Lewey bodies in neurons
Why are proteins useful as drugs?
they are adaptable
What is meant by 'proteins as therapeutics'?
using drugs that alter/correct a faulty protein
How can therapeutics alter a faulty protein?
by replacing it or introduce targets that trigger the clearing of cells with faulty proteins
How many genes in UniProt are involved in various diseases conditions?
4009
How many of the 4009 are potential drug targets?
1326
What makes 745/1326 genes approved drug as targets?
they fall into at least 1 of the 'druggable' classes
What are the druggable classes of target proteins?
they must be enzymes, transporters/ion channels or GPCRs
Where are the majority of potential drug targets found?
membrane-bound
How can the 3 druggable classes be targeted?
using small molecules, eliciting responses or using antibodies
How can antibodies be used to target the druggable classes?
can be conjugated to a drug, when antigen is recognised they're uptaken and drug
causes cell death
What are the two main types of therapeutics?
small molecules drugs or proteins attached to drugs
What needs to be known about a protein before its developed as therapeutic?
3D function, structure and mechanism of action in vitro and vivo
What does in vitro and in vivo mean?
in vitro= on the protein in isolation
in vivo= in a physiological context
What is circular dichroism used for?
looking at secondary structures of proteins
What is fluorescence of proteins used for?
What are conformational diseases?
caused by misfolded protein aggregates
What kind of diseases are most common?
polygenic
Why are most diseases polygenic?
bc they involve complex pathways
Which pathway is implicated in many diseases?
MAPK
What alterations in MAPK can cause disease?
mutations in BRAF bc its an oncogene
What is Parkinson's caused by?
mutations in alpha synuclein which has tendency to form fibrils
What do synuclein fibrils form?
aggregates known as Lewey bodies in neurons
Why are proteins useful as drugs?
they are adaptable
What is meant by 'proteins as therapeutics'?
using drugs that alter/correct a faulty protein
How can therapeutics alter a faulty protein?
by replacing it or introduce targets that trigger the clearing of cells with faulty proteins
How many genes in UniProt are involved in various diseases conditions?
4009
How many of the 4009 are potential drug targets?
1326
What makes 745/1326 genes approved drug as targets?
they fall into at least 1 of the 'druggable' classes
What are the druggable classes of target proteins?
they must be enzymes, transporters/ion channels or GPCRs
Where are the majority of potential drug targets found?
membrane-bound
How can the 3 druggable classes be targeted?
using small molecules, eliciting responses or using antibodies
How can antibodies be used to target the druggable classes?
can be conjugated to a drug, when antigen is recognised they're uptaken and drug
causes cell death
What are the two main types of therapeutics?
small molecules drugs or proteins attached to drugs
What needs to be known about a protein before its developed as therapeutic?
3D function, structure and mechanism of action in vitro and vivo
What does in vitro and in vivo mean?
in vitro= on the protein in isolation
in vivo= in a physiological context
What is circular dichroism used for?
looking at secondary structures of proteins
What is fluorescence of proteins used for?
