Peptides are short organic polymers. They are formed by amino acids residues bound to each other with peptide bonds. Peptides may have their own biological function or be a structural and functional part of a protein molecule. The common peptide definition implies that they might be naturally occurring due to synthetic functions of living organisms. Scientists can also synthesize artificial peptides using a controlled protein synthesis process.
“Peptide bonds” is a synonym of “amide bonds”. Each two amino acid residues form such covalent peptide bonds. Actually the formation of a peptide bond is a condensation reaction. During this condensation reaction, the carboxyl group of an amino acid reacts with the amino group of another amino acid molecule, which releases a water molecule (an example of dehydration synthesis reaction).
The amino acid residues in the polypeptide chain could form multiple constitutional isomers. This is so because the C-terminus differs from the N-terminus. Because of this and the fact that the polypeptides are hetero-polymers (they are build from different monomer units) even a short polypeptide could have multiple constitutional isomers. For example, even the most simple dipeptide which is made of two different amino acid residues could form at least two isomers. As you can see, phenylalanine (Phe) and aspartic acid (Asp) could form two dipeptides Phe-Asp and Asp-Phe. Just as a side note – the methyl ester of Asp-Phe isomer is actually the artificial sweetener aspartame which is 200 times sweeter than the sucrose.
Speaking about constitutional peptide isomers, a tripeptide containing 3 different amino acids can have 6 distinct isomers. Expressed with the language of statistics, this is a permutation without repetition, which has !3 = 3*2*1 = 6 possible variants. Going further, a tetrapeptide built of 4 different amino acid residues, could form 24 different constitutional isomers (or !4 = 4*3*2*1 = 24). However all natural peptides can use any of the 20 amino acids as possible building blocks. Thus the number of possible isomers is enormous! A decapeptide build up from all 20 different amino acids would total 2010 different constitutional oligomers!
Based on their macro structure, the majority of the peptides are linear hetero-polymers. This in plain English means, that the peptides are long chains of different building blocks (the amino acids). However, we can distinguish an another class of peptides based on their macro structure!
Cyclic peptides are simply polypeptide chains which form a ring structure. This ring structure could be generated by a covalent bond formed between:
- amino end and carboxyl end (head-to-tail), or
- amino end and a side chain residue (head-to-side-chain), or
- carboxy end and a side chain residue (tail-to-side-chain), or
- a residue from one side chain and a residue from another side chain (side-chain-to-side-chain)
The length of the main polypeptide chain of the cyclic peptides ranges from just two amino acid residues up to a few hundreds. Some cyclic peptides could be naturally produced by the living organisms. However, the majority of the known cyclic peptides have an artificial origin. Cyclic peptides have multiple applications both in medicine and molecular biology.
A distinctive property of cyclic peptides compared to linear peptides, is that they are extremely resistant to the process of digestion. This help them survive in the human digestive tract. Because of this, cyclic peptides serve as promising scaffolds that might incorporate an arbitrary protein functional domain of medicinal value. Thus they are attractive for designing new protein-based drugs that may be delivered orally.
Peptide Types Based On Structure
Besides the difference in their overall structure – linear vs. cyclic, the peptides could be grouped in the following types:
- Dipeptides – build of just two amino acids
- Oligopeptides – consists of between two and twenty amino acids
- Polypeptides – a single chain of more than twenty amino acids
Peptide Types Based On Origin and Function
Alternatively, we can group peptides based on how their origin:
- Peptide fragments – Usually enzymatic degradation of proteins in laboratory generate multiple peptide fragments. The process of natural protein degradation or peptide cleavage process also serve as sources of protein fragments. A great example are milk peptides which originate from the digestion of the milk protein casein.
- Peptones are also peptide fragments which are derived from animal material (milk or meat) and are products of proteolysis. The industry use them as nutrients for growing microorganisms like fungi and bacteria.
- Ribosomal peptides are products of the translation of mRNAs. Thus the ribosomal apparatus is responsible for the synthesis of this class of peptides. Usually they pass through a proteolysis, which removes some fragments from the polypeptide chain and form the mature form of the peptide. Most of these peptides are linear and they undergo additional post-translational modifications such as glycosylation, hydroxylation, phosphorylation, sulfonation and disulfide-formation. In higher organisms, ribosomal peptides function as hormones, signaling molecules and antibiotics.
- Non-ribosomal peptides are produced by a special class of synthetases which are not dependent of mRNAs and are not coupled to ribosomes. Each non-ribosomal peptide synthetase is responsible for just one type of peptide. Usually, non-ribosomal peptides form either cyclic or branched structure. This class of peptides often contain non-proteinogenic amino acids in their chains. After their synthesis, these peptides usually undergo modifications like acylation, hydroxylation, glycosylation or halogenation. Identical chains (dimers or trimers) of non-ribosomal peptides could form longer sequences, sometimes – cycles or even branched formations. Naturally occurring non-ribosomal peptides have quite diverse biological properties and pharmacological activities. Based on their properties we can group them into multiple functional classes – toxins, pigments, siderophores, antibiotics, cytostatins and immunosuppresors.