Ukon Nagai

Synthesis of a bicyclic dipeptide with the shape of β-turn central part

Abstract A bicyclic dipeptide derivative with fixed conformation simulating that of the two central amino acid residues in type II′ β-turn has been synthesized starting from L-glutamic acid and L-cysteine in short steps.

Bicyclic turned dipeptide (BTD) as a β-turn mimetic; its design, synthesis and incorporation into bioactive peptides

Abstract After reviewing the development of β-turn mimetics briefly, design, synthesis and incorporation into bioactive peptides of BTD will be mentioned. The biological activity of the BTD containing peptides and synthesis of some BTD derivatives will also be described.

Nuclear magnetic resonance study of side-chain conformation of phenylalanine residue in [Met5]-enkephalin: solvent, pH, and temperature dependence.

[Met5]-Enkephalin and N-acetylphenylalanine methylamide containing (2S,3S)-[2,3-2H2]Phe were synthesized 270 MHz 1H NMR spectra of the normal and selectively deuterated species were analysed. The lower-field and higher-field beta-proton signals of the Phe4 residue of [Met5]-enkephalin were unambiguously assigned to the pro-S and pro-R protons, respectively. The same assignments apply to N-acetylphenylalanine methylamide in polar organic solvents and in 2H2O, but the alternative assignments apply in C2HCl3. For [Met5]-enkephalin, the vicinal spin coupling constants 3JalphabetaS and 3 JalphabetaR and the rotamer populations around the Calpha-Cbeta bond were determined in a variety of solvents. From the pH and temperature dependences of rotamer populations of [Met5]-enkephalin, the side-chain conformation of the Phe residue in 2H2O solution was found to be considerably different from that in (C2H3)2SO solution. Rotamer populations of the Phe4 residue of [Met5]-enkephalin in organic solvents depend on solvent polarity. As compared with the reference model molecule of N-acetylphenylalanine methylamide, the rotamer populations of Phe4 of [Met5]-enkephalin are affected possibly by steric repulsion with other residues; the rotamer I is primarily favored but the rotamer II is appreciably destabilized in weakly polar solvents.

Nuclear magnetic resonance study of side-chain conformation of tyrosyl residue in [Met5]-enkephalin. Solvent and temperature dependence

[Met5]-Enkephalin and tyrosine methylamide containing (2S, 3S)-[2,3-2H]-tyrosine and [Met5]-enkephalin containing (2S, 3R)-[3-2H]tyrosine were synthesized. 270 MHz 1H-NMR spectra of the normal species and selectively deuterated species were analyzed. The lower field and higher field beta-proton signals of the Tyr1 residues of [Met5]-enkephalin (and tyrosine methylamide) were unambiguously assigned to the pro-S and pro-R protons, respectively, in organic solvents, but the alternative assignments apply in 1H2O. For [Met5]-enkephalin and tyrosine methylamide (model for N-terminal tyrosyl residue), the rotamer populations around the Calpha-Cbeta bond of tyrosyl residue were determined in a variety of solvents. Rotamer populations of the tyrosyl residue depend on solvent polarity. In aqueous solution, the rotamers I and II are predominant while in weakly polar solvents the rotamer I becomes predominant. For the tyrosyl residue of the dipolar form of [Met5]-enkephalin in (C2H3)2SO solution, anomalous temperature dependences of rotamer populations are observed. This anomaly is suggested to be due to the equilibrium of the folded and extended conformations of the main chain. In fact, the temperature dependences of rotamer populations become normal in the presence of 2 M NH4ClO4, which weakens the attraction between the N-terminal and C-terminal groups of the dipolar form and thus reduces the population of the folded form in (C2H3)2SO solution.

Cd spectra of DNP derivatives of aromatic α-amino acids and related compounds: DNP-aromatic rule as a method for determining absolute configuration of chiral amines of RCH(NH2)XAr type

Abstract Introduction of an aromatic group to the side-chain functional group or to the α-car☐yl group of aliphatic DNP-α-amino acids gives compounds which can be regarded as analogs of aromatic DNP-α-amino acids. DNP-aromatic rule 1 has been proved applicable to these compounds and also to the derivatives of DNP-phenylalanine homologs in which the car☐yl group is modified variously. By summarizing the compiled data extension of the DNP-aromatic rule to the DNP-derivatives of chiral amines with a general formula R-CH(NH 2 )-XAr is proposed.

Absolute configuration of an iturinic acid as determined by CD spectrum of its DNP-p-methoxyanilide

Abstract Absolute configuration of the long chain β-amino acid obtained from the hydrolysate of iturin A has been determined to be R by application of Dnp-aromatic rule. This is the first assignment for the chirality of an iturinic acid.

A method for determining absolute configuratiom of β-amino acids by CD spectra of their DNP derivatives

Abstract Aromatic β-amino acids were converted to the Dnp derivatives, and aliphatic ones to Dnp-pMA derivatives. The sign of the Cotton effect near 400 nm reflected the configuration at the β-position without exception. Thus, the relation seems to afford a new reliable method for determining the absolute configuration of β-amino acids.

IRREVERSIBLE PHOTOACTIVATION OF THE OPIATE RECEPTORS IN THE GUINEA-PIG ILEUM BY SOME ENKEPHALIN DERIVATIVES

Three new photolabile analogs of enkephalin were synthesized. All of them showed specific opioid activity on guinea pig ileum. Although their effect in the dark was completely removed by washing, UV-irradiation during perfusion with the drugs caused inhibition of contraction which lasted in part even after exhaustive washing.