Chem 455 Exam 2

Question 1

receptors

Answer 1

GPCRs, ion channels, nuclear receptors, receptor tyrosine kinases
they are often integral proteins in membranes and are chiral

Question 2

what are 2 fundamental characteristics of a receptor

Answer 2

recognition capacity and amplification

Question 3

recognition capacity

Answer 3

binding of molecules

Question 4

amplification

Answer 4

initiation of biological response

Question 5

Kd

Answer 5

measures the affinity to receptor aka is a dissociation constant and roughly represents the concentration of the drug that gives 50% drug receptor complex

(drug)(receptor)/(complex)

Question 6

Forces involved in drug receptor complex

Answer 6

molecular surfaces must be complementary
forces are usually weak and reversible
decreases in G of -5.45 kcal/mole changes binding eq from 1% to 99%

Question 7

ionic interactions

Answer 7

G = -5kcal/mol
Basic groups = His, Lys, Arg (cationic)
Acidic groups - Asp, Glu (anionic)

Question 8

ion-dipole, dipole dipole interactions

Answer 8

have charge transfer complexes

• Donor group contains pi-electrons/nonbonded electrons
• Acceptor groups have electron deficient pi-orbitals

Question 9

hydrogen bonding

Answer 9

G= -3 to -5 kcal/mol

interaction between X-H (x is electronegative) and N O or F

Question 10

Hydrophobic interaction

Answer 10

G = -.7kcal/mole per CH2-CH2
Increase in entropy of H2O decreases free energy and stabilizes it
Binding of one methyl group in hydrophobic pocket can improve binding by -1.5kcal/mole (factor of ~12) “magic methyl”
Pi-pi interactions between aryl groups

Question 11

Cation pi interaction

Answer 11

G = -.5 to -7lcal/mol

Most common is Trp but Phe, Tyr, His

Question 12

Halogen Bonding

Answer 12

G = -1 to -15kcal/mol
Covalently bonded I>B>Cl»F electron acceptors for electron rich O, N, S
Results from sigma-hole - positively charged region on the back side of the halogen along the R-X bond axis

Question 13

van der waals interactions

Answer 13

G = -.5kcl/mole per CH2/CH2

As molecules approach, temporary dipoles in one atom induce opposite dipoles in another

Question 14

Cooperativity w/ several interactions

Answer 14

Lots of weak add up to strong (once first interaction occurs, translational entropy is lost, lowering entropy loss in next)

Question 15

agonist

Answer 15

produce the same biological response as natural enzyme or ligand and show structural similarity to them
displays positive efficacy

Question 16

Antagonist

Answer 16

blocks response of particular enzyme/ligand and can show little structural similarity to natural ligand; noncompetitive and competitive binding sites
displays 0 efficacy

Question 17

Partial agonist

Answer 17

does not produce 100% of biological response as natural enzyme/ligand
displays positive efficacy

Question 18

Inverse agonist

Answer 18

produces opposite effect of natural ligand/enzyme

displays negative efficacy

Question 19

affinity

Answer 19

complexation with receptor

Question 20

efficacy

Answer 20

measure of maximum biological effect that drug can produce as a result of receptor binding; initiation of response

Question 21

Three point attachment theory

Answer 21

enantiomers cannot be distinguished by receptor by 2 binding sites- needs at least 3 sites

Question 22

atropisomerism

Answer 22

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 23

Eutomer

Answer 23

more potent enantiomer

Question 24

Distomer

Answer 24

less potent enantiomer

Question 25

Three point attachment theory

Answer 25

Enantiomers cannot be distinguished by two binding sites, receptors need at least three sites

Question 26

Advantages of enzymes

Answer 26

they can be purified more easily since they are cytosolic and membrane binding is not an issue
enzyme inhibitors can be designed from natural substrates
mechanism of enzyme can be used in design of transition state analog inhibitors