Page 124 - Medicinal Chemistry Self Assessment

Section 3 General Self Assessment Answers
2.5

Drug Binding Interactions

1. Both delapril and lisinopril are inhibitors of angiotensin converting enzyme (biological target) and as
2.5
+2
2.5 Drug Binding Interactions
other interacts with a Zn atom. Both of these interactions are critical for drug action. Do the following:
Drug Binding Interactions
a. Modify the molecules below to show the form of the active drug at physiological pH.
1. Both delapril and lisinopril are inhibitors of angiotensin converting enzyme (biological target) and as
+2of interaction possible between the carboxylic acids and the residues present
b. Identify the type
other interacts with a Zn atom. Both of these interactions are critical for drug action. Do the following:
within the biological target.
1. Both delapril and lisinopril are inhibitors of angiotensin converting enzyme (biological target) and as such
a. Modify the molecules below to show the form of the active drug at physiological pH.
are valuable drugs used in the management of hypertension. The active form of these drugs requires the
Answer:
presence of two carboxylic acids or two functional groups that can participate in similar types of interactions residues present
b. Identify the type of interaction possible between the carboxylic acids and the
at physiological pH. One of the carboxylic acids interacts with an active site arginine residue, and the other
within the biological target.
interacts with a Zn atom. Both of these interactions are critical for drug action. Do the following:
+2

a. Modify the molecules below to show the form of the active drug at physiological pH (pH=7.4).
Answer:
b. Identify the type of interaction possible between the carboxylic acids and the residues present within
N
H
the biological target. 2+ 2 CH R
Zn O N 2
Answer + NH 2
– – H
O O CH 3 O H N
2
Zn 2+ + N O 2 N CH R
N
H H O + NH 2 H
O – O CH 3 O –
+
Delapril N
N
H H O
Ionic interactions are possible between the carboxylic acids and the zinc ion and the ionized arginine
Delapril

residue.

Ionic interactions are possible between the carboxylic acids and the zinc ion and the ionized arginine
residue.
Ionic interactions are possible between the carboxylic acids and the zinc ion and the ionized arginine
residue.

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-

Lisinopril

Lisinopril

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