Cyclic peptide

Cyclic peptides can be classified according to the types of bonds that comprise the ring.

• Homodetic cyclic peptides, such as cyclosporine A, are those in which the ring is composed exclusively of normal peptide bonds (i.e. between the alpha carboxyl of one residue to the alpha amine of another). The smallest such species are 2,5-diketopiperazines,^[4] being derived from the cyclisation of a dipeptide.
• Cyclic isopeptides contain at least one non-alpha amide linkage, such as a linkage between the side chain of one residue to the alpha carboxyl group of another residue, as in microcystin and bacitracin.
• Cyclic depsipeptides, such as aureobasidin A and HUN-7293, have at least one lactone (ester) linkage in place of one of the amides. Some cyclic depsipeptides are cyclized between the C-terminal carboxyl and the side chain of a Thr or Ser residue in the chain, such as kahalalide F, theonellapeptolide, and didemnin B.
• Bicyclics such as the amanitins and the phalloidins contain a bridging group, generally between two of the side chains. In the amatoxins, this is formed as a sulfoxide bridge between the Trp and Cys residues. Other bicyclic peptides include echinomycin, triostin A, and Celogentin C.
• There are a number of bi and monocyclic peptides which are cyclized through a disulfide bond between two cysteines, oxytocin being a notable example.
• Cyclotides are a family of cysteine-rich peptides characterized by six conserved cysteines that form three disulfide bonds within the cyclic structure forming the characteristic cyclic cystine knot (CCK) that confers these peptides their characteristic 3D structure and it is believed to be greatly responsible for the stability and properties of the cyclotides.^[5]

Cyclic peptides in plants are synthesized via a two-step process; the translation of a linear peptide chain, and its subsequent formation into a cyclic structure through activities of a protease-like enzyme or other ways.^[6][7][8]

Some peptides, such as cyclotides, are gene-coded products obtained by the processing of larger precursor proteins. The generic configuration of the precursor protein consists of an endoplasmic reticulum signal sequence, a non-conserved pro-region, a highly conserved region known as the N-terminal repeat (NTR), the mature cyclotide domain and finally a short hydrophobic C-terminal tail.^[9][10]

Cyclic peptides tend to be extremely resistant to the process of digestion, making them of interest to scientists working on novel oral medications.^[11]

Examples include:

• Nonribosomal peptide
• lantibiotics, 19-37 residues and 1 to 5 'bridges'
• Split-intein circular ligation of peptides and proteins