Overview of Receptors and Antagonists in Pharmacology

how do drugs interact with targets

• bind to binding domain

• form reversible bond

• weak bonds such as hydrogen van der waals, hydrophobic, dipole-dipole,dipole-ion, ionic

molecular weight of typical drug

less than 500 daltons

lipinskis rule of 5

• molecular weight < 500 daltons

• less than 5 hydrogen bond donors

• less than 10 hydrogen bond acceptors

• log p value less than 5

which receptors reside in the cytoplasm

• nuclear receptors

• glucocorticoid receptors

advantage of reversible bond formed between drug and protein

• allows temporary effect

• repeated dosing for longer effects

how many G protein coupled receptors (GPCR) families

• 6

• largest superfamily

superfamily

• broad group of proteins related to eachother

Rhodopsin-like Family - Family A

largest group of GPCR, many receptors have many multiple subtypes, each coded by a separate gene

gene duplication

creates redundant copy of the essential gene, one copy is free to acquire mutations without compromising cell function

signal transduction

the process by which a receptor binds a molecular message and passes that information on in a different form

binding domain

the site where drugs bind to receptors

what allows drugs to have temporary effect

reversible bond

drugs that modify targets covalently

aspirin, clopidogrel, omeprazole

how do superfamilies arise

• evolved from common ancestral protein

• gene duplication

• redundant copy of essential gene

• one copy is free to acquire mutations without compromising cell function

advantages of superfamily gene duplication

• greater flexibility

• greater ability to a adapt to environment

• independent regulation

• agonist binding can change - recognition of different signalling molecules

  • more complex signalling mechanisms can evolve