Studies on self-assembling peptides containing novel amino acids with hetero-rings in side-chains

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In this research project, we have intended to develop new self-assembling peptides containing novel α,α-disubstituted glycines with hetero-rings, and investigated synthesis, conformation and Cu-complex formation of various peptides containing novel α, α-disubstituted glycines with hetero-rings, α, α-di(2-pyridyl)glycine (2Dpy), α-phenyl-α-(2-pyridyl)glycine (2Ppg), α-methyl-α-(2-pyridyl)glycine (2Pmg), α-methyl-α-(2-pyrazyl)glycine (2Pzm) and α-methyl-α-(2-thiazolyl)glycine (2Tmg).1.Tripeptides (Z-AA_1-2Dpy/2Ppg-AA_3-OMe) containing 2Dpy and 2Ppg were synthesized by the Ugi reaction. NMR analysis revealed these peptides adopt a novel conformation in which each nitrogen atom of pyridine rings forms an intramolecular hydrogen bond with a hydrogen atom of an amide bond.2.The tripeptides containing 2Dpy were synthesized by the solid-phase Ugi reaction. By this method, yields of these peptides were markedly improved, compared with yields by the solution method.3.Tripeptides containing 2Pmg … More were first synthesized by the solid-phase Ugi reaction. These tripeptides adopt a unique conformation with an intramolecular hydrogen bond between 2Pmg-NH and the pyridine nitrogen.4.The 2Dpy-containing tripeptides afforded the 2:1 complex with Cu(II) ion, and the crystal structure was clarified by X-ray analysis. Further, ESR spectrum of the complex was also studied.5.A hexapeptide containing two 2Dpy residues was synthesized. The peptide adopts an extended conformation with four intramolecular hydrogen bonds between 2Dpy-NH and a pyridine nitrogen. Complex formation of the peptide with metal ions will be investigated.6.Chirality of 2Ppg in peptides was investigated by synthesis of tri-and tetrapeptides containing 2Ppg followed by separation of the diastereomers and X-ray crystal analysis, and measurement of CD spectra.7.Tripeptides, Z-AA_1-(N-Bzl)Xaa-AA_3-OMe (Xaa=2Pzm,2Tmg), containing other hetero-rings were synthesized by the Ugi reaction. In both peptides, the intramolecular hydrogen bonding between a pyrazine nitrogen and AA_3-NH and between a thiazole nitrogen and AA_3-NH, respectively, were observed. Stabilities of the intramolecular hydrogen bonding by a pyridine nitrogen, a thiazole nitrogen and a pyrazine nitrogen are compared. Less