Drug Targets Ch 1 Flashcards
What type of cells do humans, animals, and plants have?
Eukaryotic
Nucleus
Contains the genetic blueprint (DNA).
Cytoplasm
Fluid content of the cell.
Organelle
Structures within the cell.
Mitochondria
Produce energy.
Ribosomes
Protein factories.
Rough Endoplasmic Reticulum
Location of protein synthesis for secretion.
Cell membrane components
Fluid mosaic phospholipid bilayer with hydrophobic interior studded with proteins (including glycoproteins that act as carriers or channels).
Phospholipid structure
Polar head group and two hydrophobic tails.
Drug target for lipids
Cell membrane lipids
Drug targets for protein (4)
Receptors
Enzymes
Carrier proteins
Structural proteins
Drug targets for nucleic acids
RNA, DNA
Drug targets for carbohydrates
Cell surface carbohydrates
Antigens and recognition molecules
Drug targets are usually ____________.
macromolecules
Drugs usually bind to _________ _______ , which are usually _________ pockets on the surface of the macromolecule, of target via ______________ _________ and exist in ___________ between bound and unbound states.
binding site, hydrophobic, intermolecular interactions, equilibrium
Binding groups
Functional groups on the drugs that participate in binding interactions.
Binding regions
Specific regions within the binding site that are involved in binding interactions.
Induced fit
Change in shape of binding site and drug producing a pharmacological effect.
What is the strongest weak molecular interaction and in what condition is it strongest? What weakens the interaction?
Electrostatic/ionic bond (separation between two atoms with opposite formal charges) is strongest (20-40 kJ/mol). Strongest in hydrophobic environment. Weaken by distance.
What is the second strongest intermolecular interaction? When is it strongest?
Hydrogen bonds (between electron deficient hydrogen and electron rich heteroatom). Strongest when atoms’ orbitals are lined up in 180 degree line.
HBD
Hydrogen Bond Donor-Electron deficient hydrogen atom (usually bonded to a N or O).
HBA
Hydrogen Bond Acceptor- electron rich heteroatom (usually N or O).
Carboxylate ion, phosphate ion, tertiary amine are (good, moderate, poor) HBD or HBAs?
Good HBAs
Carboxylic acid, amide oxygen, ketone, ester, ether, and alcohol are (good, moderate, poor) HBD or HBAs?
Moderate HBAs
Sulfur, fluorine, chlorine, aromatic ring, amide nitrogen, and aromatic amine are (good, moderate, poor) HBD or HBAs?
Poor HBAs
Primary ammonium ion is a (good, moderate, poor) HBD or HBAs?
Good HBD
What is the weakest intermolecular interaction? What weakens this force significantly?
Van der Waals (transient areas of low and high electron density leading to temporary dipoles in hydrophobic areas). Distance weakens van der Waals.
Dipole-dipole interactions.What weakens it?
Weak intermolecular interactions (between permanent dipole moments). Incorrect positioning of groups and distance (less significantly than van der Waals but more significantly than ionic bonds) weakens.
Ion-dipole interaction: how strong is it and what is the effect of distance on it?
Between molecule with formal charge and one with permanent dipole moment. It is stronger than dipole-dipole. Distance weakens the bond, but less than in dipole-dipole.
Induced Dipole Interactions (Example)
Formal charge of one molecule induces a charge in another (Quaternary ammonium ion and aromatic ring).
Desolvation Penalties (enthalpy and entropy)
Enthalpy: energy released by binding must be greater than energy released by solvation.
Entropy: hydrophobic forces increase disorder of water
Amphotericin B
Antifungal agent that builds hyrdophillic tunnels in the cell membrane draining cell.
Therapeutic index
Ratio of dosage causing toxic effect to dosage causing max therapeutic effect. Higher means safer.
Selective toxicity
Harmful to only some cell types.
Pharmacodynamics
Study of how a drug binds to its target molecule.
Pharmacokinetics
Study of how a drug is absorbed, distributed, and metabolized.
