Two optically active (100% enantiomeric excess) isomers of ofloxacin [(+/-)-ofloxacin; DL-8280; (+/-)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7 H-pyrido[1,2,3-de] [1,4] benzoxazine-6-carboxylic acid] were prepared by use of their optically resolved synthetic intermediates. One of the isomers, (-)-ofloxacin, was 8 to 128 times more potent in inhibiting the multiplication of gram-positive and gram-negative bacteria than the other, (+)-ofloxacin, and approximately two times more active than the racemate, (+/-)-ofloxacin.

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We have examined regions of rat IGF-binding protein-3 (IGFBP-3) important for complex formations using two kinds of deletion mutants, three kinds of chimera molecules between rat IGFBP-3 and rat IGFBP-2, and a synthetic peptide (41 residues, Glu 52 -Ala 92 ) derived from rat IGFBP-3. Solid-phase binding assays using 96-well microtiter plates were designed to quantitate the relative binding affinities. It was found that not only the IGFBP-3 derivatives with the amino-terminal, cysteine-rich domain (N domain) but also the synthetic peptide maintained affinity for IGF-II. Ternary complex formation was observed with full-length IGFBP-3 and chimera IGFBP, the carboxyl-terminal cysteine-rich domain (C domain) of which was derived from IGFBP-3, unlike the mutants lacking the C domain and the chimera IGFBPs, the C domain of which was derived from IGFBP-2. These results were confirmed by affinity crosslinking experiments. Furthermore, the IGFBP-3 derivatives that possessed the C domain of IGFBP-3 bound to the acid-labile subunit, even in the absence of IGFs. Finally, we observed sites in IGF-II important for the ternary complex formation using various IGF-II mutants. These IGF-II mutants, which contained a substitution of Tyr 27 for Leu, had extremely reduced activity. These results strongly suggest that: 1) the N domain, containing at least Glu 52 -Ala 92 , of rat IGFBP-3 is important for binding to IGF-II; 2) the C domain of IGFBP-3 is essential for binding to the acid-labile subunit both in the presence and absence of IGF-II; and 3) Tyr 27 of IGF-II is important for the ternary complex formation.

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An unidentified Streptomyces, tentatively designated as Strain H 1051-MY 10, was proved to produce viomycin and two new antibiotics. The new antibiotics were extracted from the cultured mycelia with acetone and transferred to ethyl acetate after acetone was removed in vacuo. The extracted antibiotics were separated into two components by alumina column chromatography and named carbazomycins A and B, because both antibiotics were proved to contain a carbazole nucleus. The molecular formulae of carbazomycins A and B were determined to be C16H17NO2 and C15H15NO2, respectively. Further, carbazomycin B was methylated with diazomethane to give carbazomycin A. Carbazomycins inhibited the growth of phytophathogenic fungi and further showed weak antibacterial and antiyeast activities. THE JOURNAL OF ANTIBIOTICS JULY