Biochemical interactions Flashcards
What is a receptor?
the site where a drug binds and the receptor brings about a physical response
example - cholinergic receptors and acetylcholine
What is a ligand?
ions or molecules that form a complex with the receptor
example - acetylcholine, drug
What is the difference between an agonist and an antagonist?
agonist bind to the receptor to produce a biological response
antagonist blocks the action of an agonist. it blocks the active site and binds without a response
What are the types of functional groups a protein has?
polar non-polar ionised neutral basic acidic
What are the active sites that a ligand can bind to and what are they made up of?
receptors
enzymes
- both are made up of proteins
What are the different interactions that a drug can have with functional groups lining the active site of the receptor or enzyme?
covalent (single) - strongest ionic ion-dipole hydrogen dipole-dipole hydrophobic Van der Waals - weakest
What are Van der Waals forces?
weakest type of interaction
- arise because the electron cloud associated with an atom or molecule is constantly moving so the electrons are never evenly distributed = causes unequal charge
- results in small, local, instantaneous dipoles
What affects the strength of Van der Waals forces?
the larger the surface area and the larger the number of electrons - the larger the interaction
- surface area dependent
interactions only occur when the molecules are close together
- forces drop quickly if the molecules move far apart
- they are weak and act over a short distance
What are dipole-dipole interactions?
permanent dipole-dipole interactions can occur when there is a difference in electronegativities of the atoms sharing chemical bonds
- dipoles will attract one another
bond are stronger than Van der Waals
- it is a electrostatic attraction
What is electronegativity?
tendency of an atom to attract a bonding pair of electrons to itself within the atom
What are hydrogen bonds?
formed when there are functional groups with N, S or O present and there is an H atom linked to it
- due to the electronegativity difference, the bond is polarised
- the H atom is shared between the donor (O, S or N) and the acceptor (O, S, or N)
- H atom is more strongly bonded to the donor due to the covalent bond
When are hydrogen atoms stronger? in a straight line or bent?
hydrogen bonds are directional
- they are stronger when all the atoms/bonds are in a straight line
What are ion-dipole bonds?
drugs will ionised functional groups will bind worth permanent dipoles (with an electronegativity difference)
- plays a role in water solubility of a drug
What is ionic bonding?
formed between species with opposite charges
- can act over long distances and are strong
What is covalent bonding?
majority of bonds within drugs and their targets are covalent
- are strong = drugs forming covalent bonds are usually permanently bonded to their target
What is an example of covalent bonding in drugs?
anti-cancer drugs, mechlorethamine, can alkylate DNA in tumour cells. It links the strands together.
- makes them unable to function so the cell dies
alkylation - addition of an alkyl group
What is the difference between water molecules in liquid water and in ice?
a system will adopt the lowest energy configuration - meaning it will attempt to make as many bonds as possible
liquid water molecules - H bonds are continuously forming and breaking
ice water molecules - forms 4 H bonds
- O can make 2 bonds and H can make 1 each
How does water solvate (dissolve) other molecules?
a shell of water forms around polar molecules
- stops them from interacting with one another
What is hydrophobic attraction?
water cannot bond to oil so it forms a cage around oil droplets by having H bonds with each other
- increases the energy of the system = fewer H bonds and entropy decreases
if there are two droplets
- two droplets result in the system having high energy = entropy decreased for both
make one large droplet
- releases some molecules back into the solution
- increases entropy of the solution as there are more molecules
Why is optical, geometrical and conformation isomerism important for drug binding?
optical
- drugs must be administered as single enantiomer as mirror image can have adverse effects
geometric
- rotation around a double bond
- cis = molecules on the same side, trans = molecules on opposite sides
conformational
- molecules can adopt preferred shapes
- drug binds more easily if its preferred conformation fits the active site
List the types of interactions a drug can have with an active site.
List them from the strongest to the weakest interaction.
covalent, ionic, ion-dipole, hydrogen bonding, dipole-dipole, hydrophobic and Van der Waals
What are the two key requirements necessary for hydrogen bonding to take place?
Hydrogen directly bonded to an electronegative atoms such as O, S or N, thus generating a polar bond.
An hydrogen bond acceptor, something with a lone pair or slightly negative end
