Receptor/enzymes

Drug Design Most drugs work on proteins Somehow interfere with a biochemical process –Can shut down –Can activate

Proteins Polymers of amino acids that have some function –Enzymes –Receptors

Protein structure Function very dependant on structure Polymers of amino acids Huge molecules Fold back on selves Held together by weak interactions Disruption of structure called denaturation

Hemoglobin structure example

Enzymes Biological catalysts Speed up reactions without being consumed

Enzymes often involved in metabolic pathways

Enzyme mechanism E + S  > ES  > EP  > E + P

Receptors Molecules on a cell surface Binding by “ligand” on outside of cell causes changes on the inside of the cell –Molecule brought in –Cellular signalling

Receptor binding causes change on inside of cell

Drugs Most drugs work on receptors or enzymes Problems –Receptor/enzyme works too well –Receptor/enzyme doesn’t work well enough

Lock and Key Hypothesis Protein and ligand have complementary shapes. Interactions must also be complementary –If enzyme charge is negative, substrate must be positive –If pocket is nonpolar, ligand must be nonpolar

Competitive binding Drug (I) binds instead of substrate/ligand E S I E I S

Drug binds instead of substrate Antagonists –Binding prevents substrate binding Blocks response Agonists –Binding of drug instead of substrate elicits response turns switch on

Drugs can bind to other sites “allo” binding –Can activate –Can deactivate –Can attenuate

Inhibition at allo site S I I Inhibitor binds to an allosteric site on the enzyme Changes active site so substrate doesn’t bind

Allosteric Activation Active site will not bind substrate Allosteric activator binds and changes shape of active site Now substrate binds S A A S

Antibiotics Bacteria different than human cells –Similar biochemistry

Penicillin prevents formation of bacterial cell walls

Viruses Contains DNA surrounded by protective shell or capsid Uses host cells enzymes and ribosomes for replication Lysogenic phase: viruses may remain dormant inside host cells for long periods. There is no obvious change in their host cells Can enter the lytic phase: new viruses are produced, assemble, and burst out of the host cell. The cell is killed and other cells are infected

Typical Viral structure

Lytic and lysogenic life cycles

Antivirals Interfere with some aspect of life cycle –Some with attachment –Some with self assembly –etc