How do drugs work?

Question 1

What kind of actions are drugs often involved in?

Answer 1

Most drugs are ligands that associate with a biological macromolecule target.

Question 2

What kind of macromolecules do drugs interact with usually?

Answer 2

Lipids (cell membranes)

Carbohydrates (glycoproteins, glycosphingolipids)

Nucleic acids (DNA and RNA)

Proteins (transporters, structural proteins, enzymes, and receptors)

Question 3

What does induced fit imply?

Answer 3

Conformational flexibility of drugs and target macromolecules mean that binding often is associated with shape changes

Question 4

What is the combined features of a drug that bind to a target and cause a biological effect called?

Answer 4

The pharmacophore

Question 5

What determines the position of the equilibrium between drug binding and drug dissociation from target?

Answer 5

The free energy between the 2 sides

Question 6

What is the formula for free energy of reaction between receptor and ligand using the equilibrium constant ant temperature?

Answer 6

ΔG = −RT ln(Kd)

Question 7

What is the formula for free energy of reaction between receptor and ligand using the enthalpy and entropy?

Answer 7

ΔG = ΔH - TΔS

Question 8

What is the formula for free energy of reaction between receptor and ligand using the enthalpy and entropy?

Answer 8

ΔG = ΔH - TΔS

Question 9

What is entropy?

Answer 9

Disorder. Systems tend towards disorder rather than order.

Question 10

What are the common interactions that ligands and receptors interact through?

Answer 10

Most are non-covalent and include (1/10th of the strenght of a covalent bond):

Ionic dipole

Charge - dipole

Dipole - dipole

Ion - π

π - π

Hydrogen bonds

Dispersion forces

Question 11

On what does the strength of the ionic interaction depend?

Answer 11

Strength of ionic interaction is distance dependent. If far away the polarity guides the molecule into the site of interaction. The strength of the interaction then increases as the ligand is closer to its receptor.

Strength is inversely proportional to distance.

Question 12

What is an ionic coordination complex?

Answer 12

An ionic interaction that involves a metal. It involves an overlap of orbital containing a pair of electrons with an empty orbital of metal

Question 13

Why are most biomolecules charged?

Answer 13

Due to everything occurring in solution and so charged species are more water soluble generally.

Question 14

What charge to nucleic acids typically have?

Answer 14

Phosphodiester functional groups make them negatively charged

Question 15

What are the common ionisable functional groups used in drugs?

Answer 15

Carboxylic acids and sodium salts

Question 16

What forms do polar molecules have in water?

Answer 16

They have an ionic form which makes up most of the molecules and then a neutral form which is non-polar and allows the molecule to diffuse through hydrophobic cell membranes thus shifting equilibrium towards creating more of the non-polar forms and allowing more to diffuse into the membrane.

Question 17

Are amides and alcohols ionized at pH 7?

Answer 17

No

Question 18

What affects the strength of hydrogen bonds?

Answer 18

The distance between the NOF and the H. The shorter the distance the stronger the bond.

Optimal geometry is 180 degrees and the greater the deviation the weaker the bond.

Question 19

What are salt bridges comprised of?

Answer 19

Interaction between ionic and hydrogen bonds interacting with each other

Question 20

What is the weakest type of non-covalent interaction?

Answer 20

Dispersion forces. They exist between molecules that can’t bond in other ways . Although they are very weak in individual molecules they can have strong interactions over large surfaces.

Question 21

What are dispersion forces?

Answer 21

Electron cloud not evenly distributed around nucleus at all times which means there are times of attraction between electrons and nucleus of other atom. So when they come together the net change is the movement of atoms towards each other.

Question 22

What is important for dispersion force interactions?

Answer 22

Shape complementarity due to interaction dropping off quickly