Definitions

Question 1

mechanism of action for TCIs

Answer 1

compound binds noncovalently to target protein; electrophile gets put close to the nucleophile on the protein

Question 2

ligand efficiency and TCIs

Answer 2

covalent bond binds more tightly than a noncovalent bond; the bound form is favored–> infinite ligand efficiency

Question 3

affinity

Answer 3

measure of how strongly the drug binds to its receptor

Question 4

efficacy

Answer 4

measure of max biological effect that drug can produce as a result of receptor binding

Question 5

fundamental characteristics of receptors

Answer 5

recognition capacity

amplification

Question 6

agonist

Answer 6

produce the same biological response as the natural enzyme/ligands; often show structural similarity to natural enzyme/ligand

Question 7

antagonist

Answer 7

blocks response of particular enzyme/ligand; often show little structural similarity to natural ligand

Question 8

partial agonist

Answer 8

does not produce 100% of the biological response as the natural enzyme/ligand

Question 9

inverse agonist

Answer 9

produces the opposite effect of the natural ligand/receptor

Question 10

importance of chirality in drug design

Answer 10

enantiomers cannot be recognized by only two points of attachment; need at least three points

Question 11

importance of stereospecific drug design

Answer 11

if the lead has low potency, it may be because of a low population of the active conformer

Question 12

intrinsic activity

Answer 12

max response induced by a compound relative to a reference compound

Question 13

atropisomerism

Answer 13

occurs when there is hindered rotation about a single bond as a result of steric or electron constraints; causing slow interconversion of two conformers

Question 14

two characteristics of enzymes

Answer 14

recognize substrate; catalyze reaction

Question 15

advantages to dual acting inhibitors

Answer 15

-with two drugs you would need to develop separate syntheses, two formulations, etc
-two drugs have different pharmacokinetic rates and metabolic properties
-the likelihood that two drugs will progress to the clinic at the same time is small
-

Question 16

reversible enzyme inhibitors

Answer 16

inhibition of enzyme activity that is reversible (noncovalent)

Question 17

irreversible enzyme inhibitors

Answer 17

inhibits enzyme for an extended period of time (covalent)

Question 18

competitive reversible inhibitors

Answer 18

compete with substrate for active site binding; formation of the EI complex prevents binding of the substrate

Question 19

alternative substrate inhibitors

Answer 19

alternative substrate is turned over by the enzyme so the actual substrate cannot be active upon

Question 20

affinity labeling agents

Answer 20

• reactive (potentially toxic)
• once EI complex forms, unimolecular
• if EI complex forms with other enzymes, needs nucleophile present at the active site near reactive group for reaction to occur

Question 21

mechanism based enzyme inactivators (suicide inhibitors)

Answer 21

• unreactive
• target enzyme and converts into a species that inactivates it
• inactivation occurs prior to release of activated species

Question 22

binding specificity

Answer 22

how well the enzyme recognizes the receptor and vice versa; can be broad or absolute

Question 23

specificity of reaction

Answer 23

amino acid side chains; cofactor/coenzyme interactions; prochiral hydrogens

Question 24

IC50

Answer 24

inhibitor concentration that produces 50% enzyme inhibition

Question 25

bacteriocidal

Answer 25

kills bacteria

Question 26

bacteriostatic

Answer 26

stops bacterial growth but does not kill them

Question 27

antimetabolite design

Answer 27

structures related to pyrimidines and purines interfere with biosynthetic pathways of metabolites by enzyme inhibition or by incorporation into proteins or DNA