Drug Receptor Interactions

Question 1

List the primary macromolecules that interact with molecules involved in cell signaling.

Answer 1

Signaling molecules interact with DNA, RNA, and Proteins

Question 2

Broadly describe how drug molecules produce their effects in this context

Answer 2

Drug molecules or exogenous toxins act similarly to signaling molecules by interacting at the same groups of macromolecules, often mimicking or blocking the action of the endogenous signaling molecules.

Question 3

Autocrine signaling

Answer 3

Action in the same cell (norepinephrine and cytokines.

Question 4

Paracrine Signaling

Answer 4

Action at a neighboring cell ( histamine and serotonin)

Question 5

Endocrine signaling

Answer 5

Action at a distant site (different organ or tissue)

(Insulin, glucagon, estrogen testosterone.

Question 6

Neurotransmitter Signaling

Answer 6

Act across synapses or gap junctions

acetylcholine, glutamate serotonin, norepinephrine

Question 7

Cell to cell communication

Answer 7

interaction between surface molecules (typically proteins) on cell surfaces to connect two cells resulting in a change to one or the other cell. (immune T&B cell interaction, HIV & T-cell (gp120 )

Question 8

Receptors are typically large macromolecules composed of

Answer 8

DNA, RNA is Proteins

Question 9

typical binding site has a three dimensional structure with chemical _______________ extending into a ____________________.

Answer 9

Functional groups and binding site

Question 10

The position and chemical properties of the functional groups in the binding site must match the corresponding interacting functional groups on the signaling molecule or ___________

Answer 10

Ligand

Question 11

_____________ ligand will interact optimally with only one or a small number of receptors.

Answer 11

Selective

Question 12

_____________ ligand will interact with many receptors.

Answer 12

Non-selective

Question 13

The precise match between receptor and ligand in 3D space is the basis for ____________.

Answer 13

Selectivity

Question 14

The _________ and ______model describes a type of ligand/receptor interaction that involves a precise match between the ligand and receptor in which no change in the structure of the molecule is postulated to occur

Answer 14

Lock and key

Question 15

In biochemical terms, the ligand binds with highest ________ to the receptor ____________.

Answer 15

Affinity and ground state

Question 16

The lock and key model is the simplest model for drug receptor interactions as it does not require the ligand induce a ________________________ in the receptor molecule.

Answer 16

Conformational change

Question 17

The __________ model of ligand/receptor interactions indicates that the ligand binds to a receptor but subsequently “induces” a change in conformation that results in a higher affinity binding interactions.

Answer 17

Induced fit

Question 18

IN the induced fit models the ligand does not fit the ground state of the receptors optimally but rather a new ______________.

Answer 18

Structural conformation

Question 19

The structural conformation of the receptor is presumably the “active” conformation and leads directly to the observed effects of ligand binding.

Answer 19

Just read it

Question 20

Induction of a new conformation is the result of the ligand binding more tightly to a different conformation than the ground state and thus energy of binding translates to stabilization of the new conformation.

Answer 20

READ

Question 21

Structure function relationship: The very precise interaction between the signaling molecule and the receptor is key to the ability of a ligand to produce an effect _______________.

Answer 21

Intrinsic activity

Question 22

Even slight changes can alter the ligand’s ability to produce an effect by altering the __________________ of the ligand/receptor interaction.

Answer 22

Inherent stability

Question 23

___________________________ (SAR) studies in medicinal chemistry explore the nature of the structural requirements of the receptor and ligand interaction through systematic modification of the ligand functional group positions and chemical properties.

Answer 23

Structure/ Activity Relationship

NOTE: Some compounds produced by this approach will have substantially different properties and selectivity while others will have enhanced selectivity. Both antagonists and agonists will typically be identified.

Question 24

SAR studies, often involving computer modeling of the interactions, s are fundamental to developing new drugs and contribute to a drug development approach called _______________________.

Answer 24

Rational drug design

Question 25

A typical SAR study may involve 100 or more variations of a single ______________ to fully evaluate the structural relationships.

Answer 25

Lead molecule

Question 26

A secondary approach of modifying the receptor known as _____________________ may also be employed.

Answer 26

Site directed mutagenesis

Question 27

Define Affinity

Answer 27

The strength of interaction between ligand and receptor resulting from the formation of chemical bonds between the ligand and receptor (typically non-covalent).

Question 28

Define Intrinsic activity

Answer 28

The ability of a ligand to produce an effect as a result of a conformational change in receptor structure.

Question 29

Define Intrinsic efficacy

Answer 29

similar to intrinsic activity but is defined as the ability of a drug to induce a specific level effect relative to other molecules. ‘Efficacy refers to the amount of the response produce while activity refers to the ability of a ligand to produce an effect.

Question 30

Define Agonist

Answer 30

A ligand capable of inducing a maximum functional effect on binding to a receptor.

Question 31

Define Partial Agonist

Answer 31

A ligand capable of producing a less then maximal functional effect on binding to a receptor.

Question 32

Define Antagonist

Answer 32

A ligand that binds to a receptor but is not capable of producing a functional effect.

Question 33

Define Competitive Antagonist

Answer 33

An antagonist that binds to the same binding site as an agonist and “competes” with the agonist. Competitive antagonists will appear to alter the affinity of the competing agonist but not the efficacy.

Question 34

Define Non-competitive antagonist

Answer 34

A non competitive antagonists binds to a different binding site than the agonist. Non-competitive antagonists appear to alter the efficacy of the agonist when both are present at the same time.