The base-release activity of oxygen adduct of bleomycin-Fe(ll) complex ] from DNA decreased with a half-life of 5.2 minutes, when incubated at 0°C in 0.05 M Tris-HCl buffer at pH 7.8 in the absence of DNA. Under the same condition, however, visible and ESR spectra showed that the adduct was immediately converted into the ferric complex. The ESR study further indicated the simultaneous formation of two kinds of the low-spin BLM-Fe(III) complex. One of them disappeared in parallel with the decrease of the base-release activity and transformed into the other. The latter Fe(III) complex was stable but inactive. However, by addition of hydrogen peroxide to the latter, the former was regenerated and the base-release activity appeared. Oxygen concentration measurements by oxygraph showed that one mole of BLM-Fe(II) consumed approximately 0.5 mole of molecular oxygen instantly, but did not any more thereafter in the absence of a reducing agent. While in the presence of 2-mercaptoethanol, the oxygen consumption proceeded biphasically, and equimolar oxygen was consumed by BLM-Fe(II) in the first rapid reaction.These results suggest that oxygen adduct of BLM-Fe (II) is reduced by one electron transfer from an external electron donor and the resulting BLMFe(III)-O2H-[or its deprotonated form: BLM-Fc(lll)-O22-] shows the activity to break DNA accompanying the base-release.Bleomycin (BLM) is a group of glycopeptide antitumor antibiotics discovered by UMEZAWA et al.from the culture filtrate of Streptomyces verticillaus1). The cytotoxicity of BLM has been found to be related to its ability to induce intracellular breakage of DNA2,3). DNA degradation by BLM in vitro occurs in the presence of ferrous ion and molecular oxygen, and it is promoted by addition of hydrogen peroxide and reducing agents such as 2-mercaptoethanol, dithiothreitol and ascorbic acid'4~8). BLM with ferric ion does not cause DNA degradation in the absence of a reducing agent, but does it in the presence of the reducing agent9,10). BLM forms a complex with ferrous ion") and the three-dimensional structures of BLM-Fe(II) complex and its oxygen adduct were proposed on the basis of X-ray crystal-

In this communication, the structure of P-3A Cu(II)-complex as determined by X-ray crystallographic analysis is presented. The crystals of P-3A Cu(ll)-complex as recrystallized from aqueous solutions were rhombohedral in shape and dark blue in color. As the crystals readily deteriorated in air by losing water of crystallization, they were sealed in glass capillaries prior to exposure to X-rays. A specimen of the approximate dimensions 0.2 x 0.2 x 0.25 mm was mounted on a Philips PW-1100 diffractometer and the unit cell dimensions and intensity data were measured with monochromatic (graphite plate) CuKa radiation. The cell dimensions ab17.075(9), c21.289 (I1) A, i-=120°, and the symmetry of the intensity distribution indicated that the LAUE group of the crystal must be 3 m. The space group was at first assumed to be P3,21* taking into account the LAUE group and the absent reflexions, 1=3 in 0 0 1. The density of the

No abstract

No abstract

Stereoisomers and analogues of bestatin, [(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]-L-leucine, were synthesized and tested for aminopeptidase B and leucine aminopeptidase inhibiting activity. Among the eight stereoisomers, the 2S stereoisomers exhibited strong activity. In a series of compounds in which the L-leucine residue of bestatin was substituted with other amino acids, only the one containing isoleucine showed more activity than bestatin. Norleucine, norvaline, methionine, valine, serine, glutamine, phenylalanine, glutamic acid, proline, and lysine analogues gave, in that order, decreasing activity. Alkyl and phenyl sub stitution for the benzyl group of bestatin decreased the activity markedly. p-Methyl-, p-chloro-, and p-nitrobestatins showed greater activity than bestatin.