Drug Mechanisms and Drug Resistance Flashcards
(30 cards)
Energy of ionic bond
16-28 kJ/mol
Energy of Van der Waals interaction
4 kJ/mol
Nitrogen-hydroxyl hydrogen bond energy
28 kJ/mol
Hydroxyl-oxygen hydrogen bond energy
20 kJ/mol
Amine-nitrogen hydrogen bond energy
12 kJ/mol
Amine-oxygen hydrogen bond energy
8 kJ/mol
Thioester bond energy
31 kJ/mol
Free energy of ATP hydrolysis
30 kJ/mol
Free enery of phosphocreatine hydrolysis
44 kJ/mol
ΔG from Kd
ΔG’o = - RT ln(Keq’)
Keq’ = 1 / Kd
Ergo, alternatively:
ΔG’o = RT ln(Kd)
If Kd = 1 mM, ΔG’o =
If Kd = 1 mM, ΔG’o = -17 kJ/mol
If Kd = 1 nM, ΔG’o =
If Kd = 1 nM, ΔG’o = -51 kJ/mol
If Kd = 1 μM, ΔG’o =
If Kd = 1 μM, ΔG’o = -34 kJ/mol
ΔG’o
pH = 7.00
[Components] = 1 mM
T= 25oC or 298K
P = 1 atm
R
8.314 J / mol K
A drop in Kd by one order of magnitude (e.g., by 10-3) corresponds to a change of ___ kJ/mol in ΔG’o
A drop in Kd by one order of magnitude (e.g., by 10-3) corresponds to a change of -17 kJ/mol in ΔG’o
What problem do proteases solve?
Hydrolysis of proteins is thermodynamically favorable, but kinetically extremely slow.
This is because water is a bad nucleophile and amide carbonyls are bad electrophiles.
Hydrolysis by a protease occurs at the ___ bond
Hydrolysis by a protease occurs at the scissile bond
Aspartyl protease mechanism
Protease “flaps”
Flap-peptide interaction
Classes of HIV antivirals
Actions of HIV protease
HAART
Highly active antiretroviral therapy
- Combination of drugs targeting HIV at different stages in lifecycle
- Started as early as possible after diagnosis
- Latent virus cannot be eliminated, so treatment must continue for life
