MO23 Drug-Protein Interactions Flashcards
What are 5 types of drug - protein (target) interactions?
- Cell wall structure of micro-organisms (to break and destroy)
- Proteins - enzymes
- Proteins - receptors
- Proteins - transporters
- DNA/RNA
Where are drug targets found?
- Inside cells
- cell membranes
- on the cell surface
- in the blood
What are the 3 types of interactions that are occuring when a drug and a protein interact?
- Covalent interactions
- Non-covalent interactions/intermolecular bonds
- Coordinate bonds
Describe how a covalent bond occurs in a drug-protein interaction
Drugs can interact with an ‘active site’ of an enzyme forming a covalent bond which results from the sharing of electrons between atoms. This is a new chemical bond formation that is often irreversible and very strong.
What are some examples of intermolecular (non-covalent) bonds? (7)
- Electrostatic/ionic
- H-bonding
- Van der waals/hydrophobic
- Pi stacking and pi cation
- Dipole - dipole (most interactions are this type)
- Repulsive
- Desolvation
-attractive forces are reversible
Describe electrostatic/ionic bonds and their properties
- the strongest intermolecular bond
- attraction of opposite charges usually between -ve charge from drug functional group and +ve enzyme charge.
- strength of the interaction is inversely proportional the distance and is also dependent on the environment (eg stronger in hydrophobic areas)
- most important initial interaction
Many drugs contain acids or amines which are easily ionised at physiological pH and able to form ionic bonds via the attraction of opposite charges
Describe hydrogen bonds and their properties
- attractive force between highly polar groups
- Involves a H-Bond Donor and a H-Bond Acceptor
- HBD = hydrogen linked (covalently) to an electronegative atom
- HBA = atom with NBP electrons
- an interaction of orbitals DOES occur so the direction of the bond is important. Optimally the donor H points directly at the lone pair of electrons at 180 degrees.
- moderate strength bond
Describe van der waals (hydrophobic) interactions and describe their properties
- very weak interactions
- caused because e- distribution is never even, transient areas of low and high electron densities which creates temporary dipoles. These induce the same on other molecules
- present in all molecules
What is pi stacking and the properties of this kind of intermolecular bonding?
- mainly aromatic interactions
- don’t lie directly on top of eachother, ‘offset’ as there is the greatest electron density on the face (pi orbitals) and reduced electron density on the edge.
- in DNA pi stacking causes intercalating where the drug is inserted between two other molecules in the DNA modifying the shape.
What are dipole-dipole interactions and what are the properties of this kind of bonding?
- occurs in molecules with permanent dipoles
- local dipoles are present in binding site
- charged/ionic group interacts with a dipole in a second molecule.
What are repulsive interactions and what are their properties?
- stops molecules merging with eachother
- orbitals overlap when molecules come together
- two like charges are repelled
What is desolvation and its properties?
-Drug targets (proteins/DNA) exist in an aqueous environment so the drug and macromolecule are solvated with H2O.
-both drug and target need to be stripped of their water prior to binding which requires energy (to break H bonding) = desolvation and creates less order.
What is metal ion coordination?
- changes the shape
