Section 23.9 Strategy of Peptide Bond Synthesis: N-Protection and C-Activation 9773-D Molecules:
Glutathione;
Oxidized glutathioneGlutathione is a tripeptide of glutamate, cysteine, and glycine. Its function is to de-
stroy harmful oxidizing agents in the body. Oxidizing agents are thought to be respon-
sible for some of the effects of aging and are believed to play a role in cancer
(Section 9.8). Glutathione removes oxidizing agents by reducing them. Consequently,
glutathione is oxidized, forming a disulfide bond between two glutathione molecules.
An enzyme subsequently reduces the disulfide bond, allowing glutathione to react
with more oxidizing agents.PROBLEM 22What is unusual about glutathione’s structure? (If you can’t answer this question, draw the
structure you would expect for a tripeptide of glutamate, cysteine, and glycine, and com-
pare your structure with the structure of glutathione.)23.9 Strategy of Peptide Bond Synthesis:
N-Protection and C-Activation
Because amino acids have two functional groups, a problem arises when one attempts
to make a particular peptide bond. For example, suppose you wanted to make the
dipeptide Gly-Ala. That dipeptide is only one of four possible dipeptides that could be
formed from alanine and glycine.If the amino group of the amino acid that is to be on the N-terminal end (in this
case, Gly) is protected, it will not be available to form a peptide bond. If the carboxyl
group of this same amino acid is activated before the second amino acid is added, the
amino group of the added amino acid (in this case, Ala) will react with the activatedreducing agent oxidizing agentSHCOO−CH 2+O O OH 3 NCHCH 2 CH 2 C NHCHC NHCH 2 CO−SSCOO−CH 2CH 2+OO OH 3 NCHCH 2 CH 2 C NHCHC NHCH 2 CO−COO−+O O OH 3 NCHCH 2 CH 2 C NHCHC NHCH 2 CO−2glutathioneoxidized glutathioneNHCHCO−CH 3OOH 3 NCH 2 C NHCHCO−CH 3 CH 3OOH 3 NCHC NHCH 2 CO−OOH 3 NCH 2 C NHCH 2 CO−CH 3OOH 3 NCHC++++Gly-Ala Ala-Ala Gly-Gly Ala-GlyBRUI23-959-998r2 29-03-2003 1:36 PM Page 977