Page 196 - Medicinal Chemistry Self Assessment

2.18 Levothyroxine (T ) 185
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4. T is the biologically active hormone. It interacts with the thyroid hormone receptor via hydrogen
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4. T 3 is the biologically identified in the structure evaluation grid.
bonding, ion–dipole, hydrophobic, and ionic interactions. Evaluate the ribbon diagram that shows
how T interacts with the surface of the thyroid receptor and identify the types of interactions
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possible for each of the five functional groups identified in the structure evaluation grid.
I O

H O I
OH
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H NH 2
O
I

Tri-iodo-L-thyronine

Tri-iodothyronine

Answer
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A. Phenol: OH interacts via H-bonding as the H-bond donor.
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5. T 4 is biosynthesized from L-tyrosine within derived from L-tryosine.
NOTE: The phenol OH is capable of participating as a H-bond donor and acceptor. In this case the

phenol specifically interacts with the thyroid receptor as the H-bond donor.

O
O
B. Ether: no role in binding interaction. I O O
H
N
I
2
I
OH
H
O
H 2 N C. Halogenated aromatic hydrocarbon: halogens interact via hydrophobic interaction; aromatic
OH
H OH
I
O
H
H hydrocarbon interacts via hydrophobic interactions or π-π stacking. H NH
OH
I
D. Primary amine: no role in binding interaction. H O NH 2 2
O
I
OH
I
E. Carboxylic acid: participates in ion–dipole (as the ion) or ionic interactions.
OH I
L-Tyrosine Levothyroxine
L-Tyrosine Tri-iodothyronine Levothyroxine

5. T 4 is biosynthesized from L-tyrosine within the thyroglobulin molecule and is considered an amino

acid–based hormone. Other hormones In the body are steroid-based (e.g., estrogen) or peptide-
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Answer: based (e.g., insulin). Evaluate the structure of T and justify its classification as an amino acid–based

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hormone by determining which functional groups are derived from L-tyrosine.

The biosynthesis s found in the amino acid tyrosine.

O
H N I O
2 OH H O I
H OH
A I B O H NH
I I O 2
H O OH
OH I
L-T Iyrosine O NH 2 Levothyroxine
I
Answer

Levothyroxine
The biosynthesis of levothyroxine occurs within the thyroglobulin molecule which is rich in L-tyrosine

residues. Iodination of the tyrosine units and phenolic coupling represent some of the biochemical

reactions that occur in the biosynthesis of the natural hormone. Box A is derived from L-tyrosine, as is