DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

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SECTION VII
N
O
H
N
H 2 N
O
N
H
O
OH
O
N
H
NH
Transition state peptidomimetic
protease inhibitor (saquinavir)
CHEMOTHERAPY OF MICROBIAL DISEASES
H 3 C
CH 3
CH 3
–
HN
N
O
CO
Gag or gag/pol
precursor polypeptide
HIV protease
(C 2 –axis of symmetry)
ζ
ε 1 ε 2
δ 1 δ 2
γ
βCH 2
+ H 3 N CH C O
–
pK 2 = 9.1 O pK 1 = 1.8
Phenylalanine
γ
δ
β
+ H 2 N
α
pK 2 = 11.0
C O
–
O pK 1 = 2.0
Proline
Figure 59–5. Mechanism of action of an HIV protease inhibitor. Shown here is a phenylalanine-proline target peptide sequence (in
blue) for the protease enzyme (in golden brown) with chemical structures of the native amino acids (in lower box) to emphasize
homology of their structures to that of saquinavir (at top).