Heterodetic cyclic peptides

Heterodetic cyclic peptides are peptides consisting only of amino acid residues, but the links forming the ring are not solely eupeptide bonds one or more is an isopeptide, disulfide, ester, etc. 

In addition to homodetic cyclic peptides, chemical ligation methods have been developed that lead to heterodetic cyclic peptides containing thiazolidine. 158-161 ... 

In the following discussion a selection of optimized procedures is presented for the synthesis on solid support of homodetic monocyclic and bicyclic as well as mixed homodetic/ heterodetic bicyclic peptides that contain at least one lactam ring, whereas heterodetic cyclic peptides containing other than amide bonds or peptidomimetics are not discussed here because of their unlimited diversity. 

Heterodetic cyclic peptides in which a disulfide bridge takes part in ring formation are obatined by the methods already discussed in connection with the construction of disulfide bridges between separate chains. Of course the dilution principle must be followed in order to diminish the extent of bimolec-ular reactions. 

For the synthesis of the heterodet cyclic depsipeptides, the acid chloride which had been prepared after the removal of the iV-protecting groups was most used. Recently, a mixture of acetylchlqride and acetylimidazole has been used for the cyclization of actinomycin acid to actinomycin Ci . Heterocyclic peptides containing disulphide rings have been cyclized by oxidation of the corresponding disulphydryl compounds . 

P. which contain only amino acid residues are called homomeric P., whereas P. with non-amino acid constituents are known as heteromeric P. Each of these classes is further subdivided into homodetic P., which contain only peptide bonds, and heterodetic P, which contain other bonds, e.g. ester, thioether or disulfide. Heterodetic P. possessing one or more ester bonds as hetero link are called Depsipeptides (see). The classification of depsipeptides does not accord entirely with the homomeric/heteromeric system it has arisen from the fact that the synthesis of these peptides presents rather special problems. There are two types of homomeric depsipeptides O-peptides contain ester-linked hydroxyamino acids, and they may be linear or cyclic (i. e. lactones) in S-peptides or thiodepsipep-tides, the mercapto group of a cysteine residue is acy-lated with an amino acid. Heteromeric depsipeptides contain hydroxy acids as the hetero component, and they are also known as peptolides. P. with non-amino... 

Val-CO-O-Thr-OH Heterodetic cyclic branched peptide (peptide lactone)... 

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