Hexapeptides Containing Sarcosine

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 NMR spectrum in DMSO-d of CycIo- Sarg) 119), in which all the residues are imino acid, is shown in Fig. 22. Allowing for the cis-tram isomerization of the 

Sar-Gly)2, the former three NH protons are probably intramolecularly hydrogen-bonded. Furthermore, since these resonance signals appeared at a higher magnetic field, these protons i ould be positioned so as to be shielded by a 7r-electron doud of the peptide bond at the comer of the /3-turn (56). The observation of internal NH s at higher field than external NH s can be explained in an alternative way (SS). If chloroform were used as solvent, internal and external NH s would have shown the same chemical shift. In such a polar solvent as DMSO where aU exposed NH s are 

It is under andable that three resonance signals for Qy-NH prohwi in ( ck -(Sar-Sar-Gly)2 which exhibited small temperature-induced shift changes can be ascribed to any three of ten posable conformers. If for an extreme case it is permitted to ascribe those Qy-NH signals to three C2- mmetric conformers where the equivalent two Qy-NH protons are intraimlecularly hydrogen-bonded, the portion of the C2-symmetric conformers in Cyclp-(Sar-Sar-Gly)2 amounts to 41% in DMSO. 

the conformation of Cydo-(Pro-Sar-Qy)2 (7i) in which two sarcosine residues of Cyclo-(Sar-Sar-Qy)2 were replaced by proline residues, was investigated. The 220-MHz NMR spectrum in ClXJa of Cyclo-(Pro-Sar-Gly)2 is shown in Fig. 10. 

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Conformational properties of a series of cyclic hexapeptides containing sarcosine have been described in Section 3.8.2. The interactions of these cyclic hexapeptides with metal salts will now be discussed in connection with their conformational properties (ii 9). 

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. 

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