The secondary structures of peptides beta 25-35 (the active toxic fragment) and beta 35-25 (reverse sequence and non-toxic fragment), as well as of the amidated beta (25-35)-NH2 peptide were investigated in aqueous solution and in the solid state by means of Fourier-transformed infrared spectroscopy and circular dichroism spectroscopy. The conformations of the beta 25-35 and beta 35-25 in solid state were identical and contained mostly beta-sheet structures. In solid state the amidated beta (25-35)-NH2 peptide also contained mostly beta-sheet structures. Freshly prepared aqueous solutions of the beta 25-32 (0.5 - 3.8 mM) contained a mixture of beta-sheet and random coil structures. Within 30-60 min incubation at 37 degrees C in water or in phosphate-buffered saline solution (PBS), beta 25-35 was almost fully converted to a beta-sheet structure. Decreasing the temperature from 37 degrees C to 20 degrees C decreased the rate of conversion from random coil to beta-sheet structures, 1-2 h being required for complete conversion. In contrast beta 35-25 in water or in PBS buffer had mostly a random coil structure and remained so for 6 days. The amidated beta(25-35)-NH2 peptide in water (2.7 mM) was also mostly random coil. However, when this peptide (2-2.7 mM) was dissolved in PBS (pH 7.4) or in 140 mM NaCl, a gel was formed and its conformation was mostly beta-sheet. Decreasing the concentration of beta (25-35)-NH2 peptide in 140 mM NaCl aqueous solution from 2 mM to 1 mM or below favored the conversion from beta-sheet structures to random coil structures. The beta 25-35 was toxic to PC12 cells while beta 35-25 was not. The amidated peptide beta (25-35)-NH2 was at least 500-fold less toxic than beta 25-35. Structural differences between these beta peptides in aqueous solutions may explain the difference in their respective toxicities.

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Die Tetrahydrochinolone (I) reagieren mit Natriumazid in Trichloressigsäure bei 60°C zu den 1,4‐Diazepinonen (II), von denen (IIa) mit Lithiumaluminiumhydrid zum 1,4‐Diazepin (III) reduziert wird.

Comparison of reaction products afforded by phenylguanidine derivatives withp-ketoesters or propiolic esters, respectively (synthesis of pyrimidones). -Summary.2-Anilino-imidazolines, when treated with eitherp-ketoesters or propiolic esters, yield two isomeric groups of pyrimidones. The isomerism is based on different positions of the carbonyl group in the pyrimidone ring. The mass spectra permit an unequivocal assignment of constitution I to the product formed with p-ketoesters and of constitution V t o that formed with propiolic esters.Additionally, Z-(Z-amino-anilino) -2-imidazoline (XII) when treated with methyl phenylpropiolate yields I X ; while treatment with ethyl benzoylacetate yields XI11 as an intermediate, which eliminates spontaneously one moleculc of water t o give the benzimidazole derivative XIV. Phenylguanidines (XV) add propiolic esters in the same way as do imidazoline derivatives. Photochemical cleavage of two carbon atoms with their adherent hydrogen atoms from the imidazole ring of the pyrimidones (V) leads to aminopyrimidine derivatives, e.g. XVI.Die Synthese von 2-Amino-pyrimidon-Derivaten aus Guanidinen und B-Ketoestern wurde von Bulou [l] am Beispiel der Reaktion mit 3-Amino-l,2,4-triazol als