Sarcosine Cyclic Peptides

Comprehensive investigations were also carried out later with Cyclo-(Sars) (30). 

It was found that Cyclo-(Sars) took the same conformation either in crystalline state or in solution, where the peptide bonds possessed a cis-cis-ds-trans-trans sequence. However, Cyclo-(Gly-Sar4) took a different conformation in solution from that in crystalline state. Cyclo-(Ala-Sar4) was found to assume different conformations in crystalline state and in solution, and in solution two different conformations existed concurrently. 

Cyclo-(Sarg) (70) was subjected to further investigations and was proved to assume the same conformation in crystalline state as in solution, where the peptide bond had a cis-cis-trans-trans-cis-cis-tram-tram sequence. As stated earlier, in cyclic peptides made of N-unsubstituted amino acids, formation of the /3-turn accompanied with intramolecular hydrogen bonds contributes to the stabilization of the ring struc- 

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The actinomycins, which are also produced by Streptomyces, not only kill bacteria but also are among the most potent antitumor agents known.b However, because of their extreme toxicity they are of little medicinal value. Actinomycin D, which is a specific inhibitor of RNA polymerase, contains a planar phenoxazone chromophore bearing two carboxyl groups, each one linked to an identical cyclic peptide made up of L-threonine, D-valine, L-proline, sarcosine (N-methylglycine), and L-methylvaline. 

Cyclic hexapeptides containing sarcosine residues are considered to be fairly flexible, in view of the nature of the N-CH3 peptide bond(70, US) and the ring number. The present author has synthesized a series of cyclic hexapeptides containing sarcosine residues, and investigated the relationriiip between the conformational multiplicity as studied by NMR spectroscopy and the nature of constitutive amino acid residues. 

The conformational diaracteristics of cyclic hexapeptides containing sarcosine and/or proline are summarhEed in Table 9, which have been explained in the discussions described above. Peptide bonds involvii imino acid residues can take either cis or trans form. As a consequence, cis and trans peptide bonds distribute randomly along the peptide backbone, vii such complex NMR spectra as observed for Cyclo-(Sar ), Cyclo-(Sar-Sar-cyclic hexapeptides increased (Table 9). The introduction of ycine residue reduced the conformational multiplicity of the cyclic hexapeptides. 

Dactinomycin 4.38), a bright red antibiotic isolated by Waksman and Woodruff in 1940, has an aminophenoxazine nucleus which bears two identical cyclic side-chains, each of which has one ester and five peptide linkages 4.39). The residues in each side-chain are iV-methylvaline, sarcosine, proline, valine. 

It consists of a chromogenic group which bears two identical, cyclic pentapeptide components. Several actinomycins are known they differ from each other in their peptide components. As is often the case with physiologically active peptides, uncommon amino acids e.g. sarcosine, are found as structural components. The occurrence of uncommon components and their cyclization to a ring structure protect the physiologically... 

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