Page 127 - Medicinal Chemistry Self Assessment

3. Each of the three odorant molecules drawn below produces a unique scent on interaction with the
olfactory receptors. Unlike most biological targets for drug action, olfactory receptors typically have an

Sclareol Nerolidol
(herbal scent) Vanillin (green woody scent)
116 Medicinal Chemistry Self Assessment

4. There are five basic flavors that our taste receptors detect: salty, sour, sweet, bitter, and umami

(savory). The taste receptors are located on taste buds that are on our tongue, soft palate, epiglottis,
and upper esophagus. Sour and salty flavors are mediated by ion channels, whereas sweet, bitter,
4. There are five basic flavors that our taste receptors detect: salty, sour, sweet, bitter, and umami
and umami flavors are derived from activation of the respective G-protein coupled receptor. The
(savory). The taste receptors are located on taste buds that are on our tongue, soft palate, epiglottis, and
umami receptor is activated by L-amino acids, specifically glutamate. Determine what interactions
are possible with the side chain of glutamate (at physiological pH) and then determine if any of the
following flavor molecules can interact with and activate this receptor.

CO H
2

H 2 N CO H
2

Glutamic Acid Cucumber flavor Green Pepper Flavor

O

N H
O N
H O P N N
H O O O

OH
H O

Shitaki Mushrooms
Inosinic Acid

Answer
The side chain of glutamic acid (glutamate) contains a carboxylic acid that will be ionized at physiological
pH. In its ionized form glutamic acid can participate in an ionic interaction or in an ion–dipole inter-
action (as the ion). The functional groups in both cucumber and green pepper flavor cannot partici-
pate in ionic interactions with glutamate as none of the functional groups are ionized (cationic) at
physiological pH. Ion–dipole interactions (as the dipole) are possible between glutamate and the
aldehyde found in cucumber flavor and the methyl ether found in green pepper flavor. Inosinic acid is
a component found with shitaki mushrooms that is thought to contribute to their unique flavor. Struc-
tural evaluation of this molecule reveals a phosphate that is ionized at physiological pH. This functional
group can participate in ion–dipole interactions with the umami receptor to elicit a savory flavor.

Go to Section 1.6 [Link to section 1.6 title]
Note: References to chapters are to Chapter 6 in Harrold MW and Zavod RM, Basic Concepts in Medicinal
Chemistry, American Society of Health-System Pharmacists, ©2013.