In this article we will discuss about:- 1. Classification of Peptides 2. Nomenclature of Peptides 3. Preparation and Purification 4. Study.
Contents
Classification of Peptides:
As already mentioned oligopeptides and polypeptides are distinguished depending on whether the peptide is formed by the union of less than 4 or at least 4 amino acid. Natural peptides consist of different amino acids; but one can synthesize homopeptides (triglycine, polyphenylalanine etc.).
Peptides can have different structures:
1. Linear peptides with a free NH2 at one end and a free COOH at the other.
2. Branched peptides where the branching of one or several amino acids on a linear peptide chain takes place either by the ω-carboxylic group of a dicarboxylic amino acid, or by the ε-amino group of lysine.
3. Cyclic peptides which have neither N-terminal nor C-terminal end.
4. Semi-cyclic peptides having only one end; when there is only one N-terminal end, the α-COOH of the last amino acid is linked with the ε-NH2 of an endopeptide lysine; inversely, when there is only one C-terminal end, the α-NH2 of the first amino acid is linked with the ω-COOH of an endopeptide dicarboxylic amino acid.
Nomenclature of Peptides:
An amino acid incorporated in a peptide chain loses one H (of its NH2) and one OH (of its COOH), or only one of the two if it is a terminal amino acid. This is called an amino acid “residue”; it is designated by adding the suffix “yl” to the root of the name (example: glycyl, seryl, tyrosyl etc.).
The amino acid of the N-terminal end is indicated first and then follow the others in their order of succession, all with the suffix “yl”; only the amino acid of the C-terminal end is designated by its unchanged name. Example: alanyl- valyl-phenylalanyl-isoleucine. One may also use abbreviations and write: Ala- Val-Phe-Ile.
Preparation and Purification of Peptides:
Peptides may be separated by different techniques: precipitation at the isoelectric point (minimal solubility), selective extraction by some solvents, etc.
Various methods are used for purification: crystallisation, counter-current distribution, adsorption chromatography, partition chromatography, ion exchange chromatography, electrophoresis, etc.
Study of Some Biologically Important Peptides:
1. Glutathione:
This is a tripeptide (γ-L-glutamyl-L-cysteinyl-glycine); its structure is shown in figure 1-12.
It is seen that the glutamic acid is linked with cysteine by its γ-COOH (peptidoid linkage) and its α-COOH and α-NH2 are therefore free.
Glutathione exists in reduced form (thiol) and oxidized form (where 2 molecules are linked by a disulphide bridge, as in cystine) and can thus play a role in some oxidation-reduction reactions.
2. Peptide Hormones:
Certain hormones, especially those secreted by the hypophysis and the pancreas, are peptides.
A few examples are given in the following:
A. Pituitary Hormones: Oxytocin and Vasopressin:
These two peptides have a cycle due to a disulphide bridge, and a side chain. Figure 1-13 shows that their structures are very similar. The structure of vasopressin differs from that of oxytocin only by the substitution of Ile by Phe, and of Leu by a basic amino acid (Lys or Arg depending on the animal species).
It is interesting to note that such minor structural differences cause great differences in biological activity; oxytocin stimulates the contraction of the uterine muscle whereas vasopressin increases blood pressure and has an antidiuretic action. It should be noted that in both cases there is no free terminal COOH, because the carboxyl group of the C-terminal glycine is amidified.
B. Adrenocorticotropic hormone (ACTH):
It is a hormone of the ante-hypophysis, whose main role is to stimulate the synthesis and secretion of steroid hormones by the cortical part of the adrenals. It has 39 amino acids; the first 24 amino acids form an invariable sequence where biological activity is located, but beyond the 25th, differences are animal species.
C. Insulin:
This hormone, causing a decrease in the glucose concentration of the blood, is secreted by the pancreas. Its molecular weight is about 6 000 but dimers (M.W. = 12 000) are easily formed and can further combine to form polymers of molecular weight of 24 000 or 48 000. The distinction between peptides and proteins – with an arbitrary limit at 10 000 – is obviously very artificial.
The structure of insulin is the first polypeptide structure which became known thanks to Sanger. Figure 1-14 shows that insulin has 2 chains: one A chain of 21 amino acids (free from basic amino acids) and one B chain of 30 amino acids (with basic amino acids).
There are 3 disulphide bridges: 2 inter-chain bridges and 1 intra-chain bridge. The nature of amino acids A 8, A 9, and A 10, in privileged position in the region of the intra-chain bridge, varies with the animal species.
3. Peptides with Antibiotic Activity:
A number of antibiotics produced by bacteria or other micro-organisms are of peptide nature.
In the following, we are mentioning only a few of them as examples:
i. Penicillin:
Valine and cysteine are found in penicillin (figure 1-15) but there are linkages other than the peptide linkage. The NH2 of cysteine is acylated, in most cases by the benzyl radical.
ii. Tyrocidins are cyclo-decapeptides. Tyrocidin B differs from tyrocidin A, merely by the replacement of L-Phe by L-Trp. Both have (figure 1-16):
iii. A residue of L-ornithine which is not an amino acid found in proteins.
iv. 2 residues of D-phenylalanine, an optical isomer never present in proteins.
Other antibiotics are also of peptide nature, or at least include a peptide part (gramicidins, polymyxins, bacitracins, actinomycins, etc).