A receptor is a biological molecule that yield a biological response upon interaction with a drug molecule
Classes of Receptors
Lipoproteins or glycoproteins:
The most common form of receptors
Often, firmly embedded in cell membrane or cell-organelle membrane
Their isolation may lead to structure collapse
2. Pure proteins:
Frequent drug receptors (e.g. enzymes)
3. Nucleic acids:
Important category of drug receptors
Targeted by antibiotics, antitumor agents, and steroid hormones (occasionally)
Occasionally regarded as drug targets
What is a druggable target?
A macromolecule that is intimately connected with a disease process but is not crucial to a wide range of normal biochemical processes
Bonding forces between ligands and receptors:
Dipole-Dipole Interactions (that include: hydrogen bonding, charge transfer bonding, hydrophobic bonding, and Van der Waal’s forces).
Not very common
Not very desirable (with few exceptions)
Found in cancer chemotherapy and in the inhibition of certain enzymes (rare otherwise)
Important because many of the functional groups will be in the ionized form at the physiological pH.
Effective at greater distances when compared to the other bonding types
Considerable importance in stabilizing structures by intramolecular bond formation
Not as important in intermolecular bonding in aqueous solutions. Why?
Based on electrostatic interaction between the nonbonding electron pair of a heteroatom (e.g. O, N, and S) as the donor, and the electron deficient hydrogen atom that is chemically bonded to a more electronegative atom (e.g. SH, NH, and OH).
Charge Transfer Interaction (CT)
Important in drug receptor interactions
Especially important in the interaction of antimalarials and their receptors and in the intercalation of some antibiotics with DNA
Dispersion and Van der Waal’s Interactions
Based on polarizability
Ion-dipole attractive forces, dipole-dipole interactions are weaker bonds (in comparison the covalent and ionic bonds)
Important because of their large numbers between drugs and receptors
Play an important role in:
Stabilizing the conformations of proteins
Transport of lipids by plasma membranes
Binding of steroids to their receptors
Also explains the low solubility of hydrocarbons in water. How?
Definitions of Classical Binding Terms for Drug-Receptor Interactions
Substance that interact with a specific cellular constituent, the receptor, and elicit an observable biological response.
May be endogenous (e.g. hormone) or exogenous (e. g synthetic drug).
2. Partial Agonists:
Act on the same messenger as other agonists in a group of ligands.
Regardless of their dose, they can not produce the same maximal biological response as the full agonist
Proportionality constant of the ability of the agonist to activate the receptor as compared to the maximally active compound in the series being studied.
Has a maximum value of unity for full agonists and a minimum value of zero for antagonists.
Inhibits the effect of an antagonist but has no biological activity of its own in that particular system.
I. Antagonists Acting at the Binding Site:
II. Antagonists acting indirectly on the binding site
Antagonism by umbrella effect
4. Inverse Agonists:
Also known as negative antagonists
Inverse agonist act at the same receptor as an agonist yet produces an opposite effect
Distinction between antagonists and inverse agonists is important.