New amino acid from the antibiotic, ristomycin A]

A new amino acid E was isolated from a mixture of the products of the reductive hydrolysis of ristomycin A 57% HJ in the presence of red phosphorus. Its characterization was performed. The new amino acid was formed as a result of reductive dehydration of the respective beta-oxyamino acid present in the native antibiotic and being completely destroyed during general acid or alkaline hydrolysis.     

The structure of antibiotic eremomycin B

A new biologically active component, antibiotic eremomycin B, was isolated from the culture liquid of Amycolatopsis orientalis subsp. eremomycini, the producing strain for antibiotic eremomycin. Its structure was established by NMR spectroscopy and mass spectrometry. Eremomycin B was shown to differ from eremomycin by the presence of an N-carboxymethyl substituent in the disaccharide eremosamine fragment.     

The crystal and molecular structure of the alpha-helical nonapeptide antibiotic leucinostatin A

The crystal and molecular structure of the nonapeptide antibiotic leucinostatin A, containing some uncommon amino acids and three Aib residues, has been determined by x-ray diffraction analysis. The molecule crystallizes in the orthorhombic space group P2(1)2(1)2(1), a = 10.924, b = 17.810, c = 40.50 A, C62H111N11O13, HCl.H2O, Z = 4. The peptide backbone folds in a regular right-handed alpha-helix conformation, with six intramolecular i----(i + 4) hydrogen bonds, forming C13 rings. The nonapeptide chain includes at the C end an unusual beta-Ala residue, which also adopts the helical structure of the other eight residues. In the crystal the helices are linked head to tail by electrostatic and hydrogen-bond interactions, forming continuous helical rods. The crystal packing is formed by adjacent parallel and antiparallel helical rods. Between adjacent parallel helical columns there are only van der Waals contacts, while between adjacent antiparallel helical columns hydrogen-bond interactions are formed.     

The structure of the aglycon of eremomycin--a new antibiotic of the polycyclic glycopeptide group

Eremomycin is shown to be a new representative of the group of polycyclic glycopeptides. By the amino acid composition it is close to vancomycin but by the structure of triphenoxytriaminotricarboxylic acid it differs from vancomycin. Monodechlorovancomycinic acid was detected in eremomycin. On the basis of the data obtained in studies on the amino acid sequence and the molecule functional groups the structural formula of eremomycin aglycon was assigned. It is demonstrated that the chlorine-containing phenylserine fragment of monodechlorovancomycin acid is located in the N-end region of the aglycon peptide chain.     

The structure and antimicrobial activity of the partial degradation products of the antibiotic eremomycin

Antimicrobial activity of partial degradation products of eremomycin, a new glycopeptide antibiotic, was studied. The products formed by eremomycin deglycosylation (deseremosaminyl eremomycin, eremosaminyl aglycone and aglycone) and elimination of the chlorine atom from the molecule aglycone moiety (dechloroeremomycin). The spectral data in favour of the compounds structure are presented. It was found that partial degradation led to a decrease in the antimicrobial activity of the antibiotic. Dechloreremomycin had the highest activity among the products. Its MIC for the methicillin-resistant strains of Staphylococcus aureus was only twice as low as that of the initial antibiotic.     

The structure of eremomycin, a new antibiotic of the group of polycyclic glycopeptides

Structure of the carbohydrate moiety of the eremomycin molecule was assessed. Two residues of eremosamine were detected in the antibiotic. One of them in the composition of 2-0-(L-eremosaminyl)-D-glucopyrazone dissaccharide was linked by the phenol group to monodechlorvancomycinic acid and the other formed the monosaccharide branch by the alcohol group of the same acid at the peptide C-end area. On the basis of the results of the present study and the data published earlier (structure of the aglycone and aminosugar) the structure of eremomycin was assigned.     

Chemical modification of ristomycin A with bifunctional reagents

Various bifunctional reagents by the free NH2 group of ristomycinic acid of ristomycin A were used for selective chemical modification of the antibiotic. The bifunctional reagents were the following: di-N-hydroxysuccinimide ether of suberic acid and 4,4'-difluoro-3,3'-dinitrodiphenylsulfone. Bis-N,N'-derivatives of ristomycin A were prepared using these reagents. The derivatives inhibited the growth of Bac. subtilis but the concentrations required for the inhibition were 2-4 times higher than those of ristomycin A. It was noted that the MIC of the bis-N,N'-derivatives depended on the length and flexibility of the "binding foot". The MIC of the bis-N,N'-derivative prepared with using suberic acid was 2 times higher than that of the derivative prepared with the use of 4,4'-difluoro-3,3'-dinitrodiphenylsulfone.     

Effect of ristomycin on the electrokinetic properties of Staphylococcus aureus cells

The electrophoretic mobility of the cells of Staph. aureus cultivated on the medium with ristomycin is markedly decreased at pH 3.0-5.0. This indicates that ristomycin added to the cultivation medium lowers the number of the phosphate groups in teichoic acids of the staphylococcal cell wall. The effect of ristomycin on the cells of the staphylococci was studied in vitro during the process of their incubation. It was shown that almost within the first minutes of the incubation ristomycin interacts immediately with the ionogenic groups of the cell wall and first of all with the phosphate groups of teichoic acids.