Download PEPTIDE BONDS AND PEPTIDES The linkage formed between

PEPTIDE BONDS AND PEPTIDES
The linkage formed between amino acids is an amide bond called a peptide bond (Figure 1). This
linkage can be thought of as the product of a simple condensation reaction between the α-carboxyl
group of one amino acid and the α-amino group of another. A water molecule is lost from the
condensing amino acids in the reaction. Linked amino acids in a polypeptide chain are called amino
acid residues. The names of residues are formed by replacing the ending -ine or -ate with -yl. For
example, a glycine residue in a polypeptide is called glycyl and a glutamate residue is called glutamyl.
In the cases of asparagine, glutamine, and cysteine, -yl replaces the final -e to form asparaginyl,
glutaminyl, and cysteinyl, respectively. The -yl ending indicates that the residue is an acyl unit (a
structure that lacks the hydroxyl of the carboxyl group).
The free amino group and free carboxyl group at the opposite ends of a peptide chain are called the Nterminus (amino terminus) and the C-terminus (carboxyl terminus), respectively. At neutral pH each
terminus carries an ionic charge. By convention, amino acid residues in a peptide chain are numbered
from the N-terminus to the C-terminus and are usually written from left to right. This convention
corresponds to the direction of protein synthesis. Synthesis begins with the N-terminal amino acid—
almost always methionine—and proceeds sequentially toward the C-terminus by adding one residue
at a time.
Both the standard three-letter abbreviations for the amino acids (e.g., Gly–Arg–Phe–Ala–Lys) and the
one-letter abbreviations (e.g., GRFAK) are used to describe the sequence of amino acid residues in
peptides and polypeptides. It’s important to know both abbreviation systems. The terms dipeptide,
tripeptide, oligopeptide, and polypeptide refer to chains of two, three, several (up to about 20), and
many (usually more than 20) amino acid residues, respectively. A dipeptide contains one peptide bond,
a tripeptide contains two peptide bonds, and so on.
Classwork
Write the structures of the following peptides:
1. Cysteinyl- Glutamyl-Valine
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Figure 1: Peptide bond between two amino acids.
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BCH 2102 – Structure and Chemistry of Biomolecules
2.
3.
4.
5.
6.
Alanyl-Asparaginyl- Methionine
Glutaminyl- Serinyl-Aspartic acid
Glutaminyl-Cysteinyl–Valine
Asparaginyl-Glutamyl-Methionine
Serinyl-Glutamyl-Aspartic acid
Some peptides are important biological compounds and the chemistry of peptides is an active area of
research. Several hormones are peptides; for example, endorphins are the naturally occurring
molecules that modulate pain in vertebrates. Some very simple peptides are useful as food additives;
for example, the sweetening agent aspartame is the methyl ester of aspartylphenylalanine (Figure 2).
Aspartame is about 200 times sweeter than table sugar and is widely used in diet drinks. There are also
many peptide toxins such as those found in snake venom and poisonous mushrooms.
Figure 2: Structure of Aspartame
An example of a naturally occurring dipeptide is carnosine, which is found in muscle tissue. This
compound, which has the alternative name β-alanyl-lhistidine, has an interesting structural feature.
The N-terminal amino acid residue, β-alanine, is structurally different from the α-amino acids we have
seen up to now. As the name implies, the amino group is bonded to the third or β-carbon of the alanine
(Figure 3).
Figure 3: Structure of Carnosine and its constituent β-alanine
Glutathione is a commonly occurring tripeptide; it has considerable physiological importance because
it is a scavenger for oxidizing agents. In terms of its amino acid composition and bonding order, it is
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SMALL PEPTIDES WITH PHYSIOLOGICAL ACTIVITY
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BCH 2102 – Structure and Chemistry of Biomolecules
γ-glutamyl-L-cysteinylglycine (Figure 4). The letter γ (gamma) is the third letter in the Greek
alphabet; in this notation, it refers to the third carbon atom in the molecule, counting the one bonded
to the amino group as the first. In this case, the γ-carboxyl group (the side-chain carboxyl group) of
the glutamic acid is involved in the peptide bond; the amino group of the cysteine is bonded to it. The
carboxyl group of the cysteine is bonded, in turn, to the amino group of the glycine. The carboxyl
group of the glycine forms the other end of the molecule, the C-terminal end. The glutathione molecule
shown in Figure 5a is the reduced form. It scavenges oxidizing agents by reacting with them. The
oxidized form of glutathione is generated from two molecules of the reduced peptide by forming a
disulfide bond between the -SH groups of the two cysteine residues (Figure 5b).
(a) Reduced glutathione (GSH)
(b) Oxidised glutathione (GSSG)
Figure 5: The oxidation and reduction of glutathione.
Two pentapeptides found in the brain are known as enkephalins, naturally occurring analgesics (pain
relievers). The two peptides in question, leucine enkephalin and methionine enkephalin, differ only in
their C-terminal amino acids.
Figure 6:
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Figure 4: Structure of glutathione
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BCH 2102 – Structure and Chemistry of Biomolecules
Some important peptides have cyclic structures. Two well-known examples with many structural
features in common are oxytocin and vasopressin (Figure 7). In each, there is an –S-S- bond similar
to that in the oxidized form of glutathione. The disulfide bond is responsible for the cyclic structure.
Each of these peptides contains nine amino acid residues, each has an amide group (rather than a free
carboxyl group) at the C-terminal end, and each has a disulphide link between cysteine residues at
positions 1 and 6. The difference between these two peptides is that oxytocin has an isoleucine residue
at position 3 and a leucine residue at position 8, and vasopressin has a phenylalanine residue at position
3 and an arginine residue at position 8. Both of these peptides have considerable physiological
importance as hormones.
In some other peptides, the cyclic structure is formed by the peptide bonds themselves. Two cyclic
decapeptides (peptides containing 10 amino acid residues) produced by the bacterium Bacillus brevis
are interesting examples. Both of these peptides, gramicidin S and tyrocidine A, are antibiotics, and
both contain D-amino acids as well as the more usual L-amino acids (Figure 8). In addition, both
contain the amino acid ornithine (Orn), which does not occur in proteins, but which does play a role
as a metabolic intermediate in several common pathways.
Figure 8: Structures of ornithine, gramicidin S, and tyrocidine A.
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Figure 7: Structures of oxytocin and vasopressin.
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BCH 2102 – Structure and Chemistry of Biomolecules
REFERENCES AND FURTHER READINGS
Moran LA, Horton HR, Scrimgeour, KG, and Perry MD (2012) Principles of Biochemistry 5th
Edn, Pearson Education, Inc., Boston, USA.
2.
Murray RK, Bender DA, Botham KM, Kennelly PJ, Rodwell VW, and Weil PA. (2009) Harper’s
Illustrated Biochemistry 28th Edn 2009 by The McGraw-Hill Companies, Inc. New York, USA
3.
Voet D and Voet JG (2011) Biochemistry 4th Edn John Wiley & Sons, Inc., Hoboken, NJ USA.
4.
5.
Garrett, R. H. and Grisham, C. M. (2013) Biochemistry 5th Edn Brooks/Cole, Belmont, USA
Biochemistry, 2012, 7th Edition, Mary K. Campbell, Shawn O. Farrell, Brooks/Cole
20 Davis Drive, Belmont, CA 94002-3098, USA
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BCH 2102 – Structure and Chemistry of Biomolecules