Studies on cyclic peptides. IV. Conformation of cyclo(Sar‐Sar‐Gly)₂, cyclo(Sar)₆ and cyclo(Sar‐Gly‐Gly)₂ and their conformational change induced by alkali thiocyanates

Abstract

SynopsisConformation of cyclo(Sar-Sar-Gly)z, cyclo(Sar)fi, and cyclo(Sar-Gly-Gly), was investigated by nmr spectroscopy. cyclo(Sar-Sar-Gly)z and cyclo(Sar)e, were shown to assume various conformations in dimethylsulfoxide. It was attributed to the distribution of cis as well as trans Gly-Sar or Sar-Sar amide links along the peptide backbone. In particular, cyclo(SarSar-Gly)Z took five or six different conformations: one or three Cz-symmetric conformations and four or three asymmetric conformations, respectively. Three of nine NH resonance signals were ascribed to the internally hydrogen-bonded glycine residues. cyclo(Sar-Sar-Gly)z and cyclo(Sar)6 showed a spectral change on the addition of alkali thiocyanates, indicating a conformational change induced by a complex formation with the alkali cations. The complex nmr spectrum due to a hybridization of different conformations changed with the salt addition into a simple nmr spectrum, suggesting a preponderence of a new, single conformation. On the basis of the spectral change, the strength for the cations binding the cyclic peptides was found to be in the order of K+ > Na+ > Rb+ > Cs+ for cyclo(Sar-Sar-Gly), and K+ > Rb+ > Cs+ for cyclo(Sar),j. On the other hand, cyclo(Sar-Gly-Gly)z in dimethylsulfoxide assumed a single Cz conformation having two glycyl peptide protons shielded from solvent and the other two exposed to solvent. This conformation did not change with the salt addition. Finally, the conformations of several cyclic peptides containing the sarcosine residue such as cyclo(Sar)c, cyclo(Sar-Sar-Gly)z, cyclo(Pro-Sar-Gly)z, and cyclo(Sar-Gly-Gly)n were compared. It appeared that proline and glycine residues reduced the conformational multiplicity of the cyclic peptide backbone, and the ability to bind alkali metal cations decreased in the above order.

Synthesis and Characterization of Poly(N-cyanoethylglycine)

“…Since the cis content of poly(Nalkylglycine) is closely related to the bulkiness of the N-substituent, 18 the estimated cis content of poly(N-cyanoethylglycine) is reasonable. The occurrence of cis and trans peptide bonds in poly(N-cyanoethylglycine) makes the whole molecule fl.exible 4 and allows the polymer to assume a compact conformation. 5 These conformational features of poly(N-cyanoethylglycine) are promising for the design of a functional polymer to bind and transport small molecules effectively.…”

“…2 ' 3 This property of poly(N-alkylamino acid)s allows different conformational states to be possible and renders flexibility. 4 Furthermore, the participation of cis amide bond makes the polymer structure somewhat more compact. 5 If the hydrogenated poly(N-cyanoethylglycine), that is, poly(N-3-aminopropylglycine), is an initiator for the polymerizations of a-amino acid NCA's carrying different functional substituents, the resulting branched poly( a-amino acid) should be differently functionalized along a flexible and compact chain.…”