A novel intramolecular hydrogen bonding between a side-chain pyridine ring and an amide hydrogen of the peptide backbone in tripeptides containing the new amino acid, alpha,alpha-di(2-pyridyl)glycine

Four tripeptides (Z-AA1-2Dpy-AA3-OMe; AA1, AA3 = Gly, Aib) containing a novel amino acid, alpha, alpha-di(2-pyridyl)glycine (2Dpy), were synthesized by the modified Ugi reaction. NMR analysis clearly indicated that the 2Dpy-containing tripeptides except the peptide in which AA1, AA3 = Aib, adopt a unique conformation with two intramolecular hydrogen bonds between 2Dpy-NH and a pyridine nitrogen and between AA3-NH and another pyridine nitrogen. This conformation has so far not been reported. On the other hand, the peptide Z-Aib-2Dpy-Aib-OMe probably adopts a beta-turn structure which is stabilized by two intramolecular hydrogen bonds between 2Dpy-NH and a pyridine nitrogen and between AA3-NH and the C=O of the Z group.     

Sharp Distortion Estimate for Locally Schlicht Bloch Functions

Let B be the space of locally schlicht Bloch functions f whichare analytic in the unit disc with f(0) = f'(0) – 1 =0 satisfying 0 < |f'(z)|(1 – |z|²) 1. For each fixedz₀ we shall determine the shape of the set {logf'(z₀): fB},that is, we shall give the sharp distortion estimate for locallyschilcht Bloch functions.     

Comparison of cross-reactivities of imipenem and other beta-lactam antibiotics by delayed-type hypersensitivity reaction in guinea pigs

The cross-reactivity of imipenem (IPM) in a delayed-type hypersensitivity (DTH) reaction was investigated by intradermal skin reaction, macrophage migration inhibition tests (MIT) and lymphocyte stimulation tests (LST) in guinea pigs. The animals were immunized with IPM, ampicillin (ABPC) or cephalexin (CEX) using Freund's complete adjuvant. Three sensitized-drugs exhibited the same immunogenicity in the skin reaction. The cross-reactivities in skin reaction among IPM, sulbactam, aztreonam, ABPC and 6-aminopenicillanic acid as penam, and CEX, ceftizoxime, 7-aminocephalosporanic acid as cephem were examined. IPM did not show cross-reactions with any of the tested drugs in three sensitized groups, indicating that the drugs possessed no cross-reactivity with tested beta-lactams in DTH. In MIT, 4 or 5 of 6 animals reacted to be sensitized drugs in each group. The cross-reactivity of IPM- and ABPC-sensitized groups in MIT was similar to that of a skin reaction, however, the CEX-sensitized animals showed broad cross-reactions. Using a kind of test drug, one or two animals in the ABPC-sensitized group showed migration enhancement, but IPM- or CEX-sensitized animals did not exhibit migration enhancement. In LST, most of the animals tested exhibited lymphocyte prolifration by sensitized drugs but a cross-reaction was scarcely observed. The above results suggest that among beta-lactams, IPM has a very low cross-reactivity. LST is considered to be more a useful assay than MIT for in vitro identification of causative drugs in animal models.     

New insulinomimetic zinc(II) complexes of alpha-amino acids and their derivatives with Zn(N2O2) coordination mode

Zinc(II) complexes of alpha-amino acids and their derivatives with a Zn(N2O2) coordination mode were found to have in vitro insulinomimetic activity as estimated with the inhibition of free fatty acid release in isolated rat adipocytes treated with epinephrine. It was revealed that the insulinomimetic activities of zinc(II) complexes with over-all stability constants (log beta) less than 10.5 are higher than those of ZnSO4 and VOSO4. The high blood glucose level of KK-Ay mice with type 2 diabetes mellitus was lowered by daily intraperitoneal injections of a zinc(II) complex, cis-[Zn(L-Thr)2(H2O)2], for 14 d. The improvement of diabetes mellitus was confirmed with the oral glucose tolerance test.     

Complex formations of silver(I) trifluoroacetate and trifluoromethanesulfonate with benzene and cyclohexene

An apparatus for measurements of equilibrium ligand vapor pressure has been applied in order to determine the stoichiometry of benzene and cyclohexene complexes of silver(I) trifluoroacetate (AgCF₃CO₂) and silver(I) trifluoromethanesulfonate (silver(I) triflate, AgCF₃SO₃) in the solid state. It has been found that the equilibrium leads the formation of such complexes as: (AgCF₃CO₂)₂(C₆H₆), (AgCF₃CO₂)₂(C₆H₁₀), (AgCF₃CO₂)₂(C₆H₁₀)₃, (AgCF₃SO₃)₂(C₆H₆), (AgCF₃SO₃)(C₆H₆), (AgCF₃SO₃)(C₆H₁₀) and (AgCF₃SO₃)(C₆H₁₀)₂. The temperature dependence of the gas-solid equilibrium ligand pressure has also been examined for these complexes, and the enthalpy and entropy changes according to the following complex dissociation reactions were estimated: (AgCF₃CO₂)L_m (s) AgCF₃CO₂ (s)+mL (g): and (AgCF₃SO₃)L_n (s) AgCF₃SO₃ (s)+nL (g), where L's are benzene and cyclohexene. On the basis of the thermodynamic data obtained, the effects of the counter anion as well as the ligand on the complex stability are discussed.     

Separation of peptides by multimode chromatography on a column packed with vinyl alcohol copolymer gel

Several mechanisms of peptide separation in high-performance liquid chromatography were observed to occur on the Asahipak GS-320 packed with vinyl alcohol copolymer. Neutral rather than acidic mobile phases were employed as they were found to result in higher retention of many peptides on the GS-320. For neutral peptides, the retention volume corresponded to the Rekker's hydrophobic fragmental constant, with a correlation coefficient of 0.71. Peptides with acidic residues eluted early, as an effect of ionic exclusion; those with basic residues were retained longer, owing to an ion-exchange effect. The ionic interactions were shown to involve the carboxylic group present on the gel polymer. The net result was found to be excellent separation of hydrophilic as well as hydrophobic peptides, related to differences in their isoelectric points. The combination of these complex mechanisms, together with the size-exclusion effect of the GS-320 gel for separation of proteins and other large molecules and for analysis with a mobile phase high in acetonitrile content, makes possible high-resolution isocratic analysis of peptides, which cannot be achieved on octadecylsilica or ion-exchange columns.