Topic 2 - Affinity Flashcards

1
Q

When do drugs have an effect on a protein

A

When they are bound the protein is modified

Effect can still persist even when ligand leaves

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2
Q

What does binding affinity depend on

A

Higher number of complimentary interactions the more tighter the bond

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3
Q

Complimentary Interactions

A

Positive with Negative
Hydrophobic Interactions
Correct size and shape

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4
Q

What happens at equilibrium (Affinity)

A

Unbound Protein x Ligand will equal Complex

Or

Dissociation Rate Constant / Association Rate Constant

Or

Kd

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5
Q

What is Kd

A

A numerical value that represents the binding affinity the ligand has for a specific protein

The concentration of ligand needed to bind 50% of total receptors

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6
Q

What would an equilibrium of 2nm mean

A

At any given moment 2nm of receptors are bound.
Kon = Koff
When one complex dissociates another associates

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7
Q

Effects of:
Smaller Koff
Same Kon

A

Smaller Koff = Slower Koff
Ligand remains bound for longer

  • More targets will be bound at equilibrium
  • Takes longer to reach equilibrium

Lower Kd (Koff/Kon)

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8
Q

Effects of:
Same Koff
Larger Kon

A

Larger Kon = Faster Kon
Ligand in area is more likely to bind

  • More targets will be bound at equilibrium
  • Takes less time to reach equilibrium
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9
Q

What does a small Kd mean

A

More tightly the ligand binds
Higher affinity

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10
Q

What kind of graph is a Kd graph

A

Hyperbolic

Will be sigmoid on a log graph

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11
Q

How is concentration of ligand and targets bound related

A

The higher the concentration the more complexes formed

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12
Q

Slow off drug (What is it)

A

Drugs that remain bound for a long time

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13
Q

Slow off drug (Binding Equilibrium)

A

Takes a long time to reach binding equilibrium

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14
Q

Slow off drug (Effect on pharmacokinetics)

A

Drug can continue to have an effect even when most of the dose has left the body

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15
Q

Fast on drug (What is it)

A

Drugs that have a high likelihood of binding

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16
Q

Fast on drug (Binding Equilibrium)

A

Reaches equilibrium faster

17
Q

Fast on drug (Pharmokinetics)

A

When dissociating a fast on drug is likely to re-associate and rebind
Fast on drugs can remain effective even when dose has already left the body

18
Q

Fast on drug (Uses for Rebinding)

A

Enhances selectivity for a target

Ex. A drug can have the same Kd for two targets, but, the ratios of Koff:Kon may be different

The one with the higher Kon will have constant rebinding to the preferred target and thus, will limit side effects