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Biomedical subjects

J B McAlpine

Publications and source records attributed to J B McAlpine.

At least 37 records · Page 2Linked to original sources
PubMed1993

5-N-acetylardeemin, a novel heterocyclic compound which reverses multiple drug resistance in tumor cells. I. Taxonomy and fermentation of the producing organism and biological activity.

The ardeemins are a new family of secondary metabolites produced by submerged fermentation of a fungus which was isolated from a soil sample collected in Brazil. Based on taxonomic studies, the producing culture was identified as Aspergillus fischeri var. brasiliensis strain AB 1826M-35. 5-N-Acetylardeemin potentiated the cytotoxicity of the anticancer agent vinblastine in multidrug resistant human tumor cells.

Antibiotics, Antineoplastic↗
PubMed1993

5-N-acetylardeemin, a novel heterocyclic compound which reverses multiple drug resistance in tumor cells. II. Isolation and elucidation of the structure of 5-N-acetylardeemin and two congeners.

A family of novel compounds has been detected and isolated following an assay for the attenuation of multiple drug resistance in tumor cells from the fermentation broth and mycelia of a strain of Aspergillus fischeri which we have designated var. brasiliensis. The structures of three components were determined employing 1-D and 2-D homonuclear and heteronuclear NMR spectroscopy and mass spectrometry. The structure of 5-N-acetylardeemin was confirmed by single crystal X-ray diffraction. These compounds are most closely structurally related to asperlicin E1).

Antibiotics, Antineoplastic↗
PubMed1993

Calbistrins, novel antifungal agents produced by Penicillium restrictum. II. Isolation and elucidation of structure.

The novel antifungal agents, calbistrins A, B, C and D have been isolated from a strain of Penicillium restrictum (AB 1875C-28). The four congeners were separated by bioactivity directed fractionation using countercurrent chromatography and preparative-HPLC. NMR studies revealed that the calbistrins each contain a carboxylic acid conjugated tetraene attached through an aliphatic ester linkage to a hexahydronaphthalene system.

Antifungal Agents↗
PubMed1992

Biosynthesis of the erythromycin macrolactone and a rational approach for producing hybrid macrolides.

The three eryA genes involved in the formation of the polyketide portion of the macrolide antibiotic erythromycin in Saccharopolyspora erythraea, appear to be organized in a single transcriptional unit on the basis of the results of gene disruption experiments. An insertion sequence-like element of lower G + C content separates eryAI from eryAII. The organization of the enzymatic domains present in the eryA-encoded multifunctional polypeptides, determined by computer-assisted analysis, is presented. This has enabled the determination of a putative dehydratase domain. A rational approach for producing novel macrolides by introducing selected changes in polyketide synthase genes is outlined. The isolation of a lactone intermediate resulting from an early synthesis step in macrolactone formation is also presented.

Amino Acid Sequence↗
PubMed1992

A colorimetric microassay for the detection of agents that interact with DNA.

A simple microtiter assay for the detection of compounds that bind DNA is described. Agents that displace methyl green from DNA are detected spectrophotometrically by a decrease in absorbance at 630 nm. The feasibility of using the assay for detecting DNA-active compounds in fermentation extracts was assessed, and the activities of reference compounds in the methyl green assay and an ethidium bromide displacement method were compared.

Aminoglycosides↗
PubMed1991

Modular organization of genes required for complex polyketide biosynthesis.

In Saccharopolyspora erythraea, the genes that govern synthesis of the polyketide portion of the macrolide antibiotic erythromycin are organized in six repeated units that encode fatty acid synthase (FAS)-like activities. Each repeated unit is designated a module, and two modules are contained in a single open reading frame. A model for the synthesis of this complex polyketide is proposed, where each module encodes a functional synthase unit and each synthase unit participates specifically in one of the six FAS-like elongation steps required for formation of the polyketide. In addition, genetic organization and biochemical order of events appear to be colinear. Evidence for the model is provided by construction of a selected mutant and by isolation of a polyketide of predicted structure.

Amino Acid Sequence↗
PubMed1991

An erythromycin derivative produced by targeted gene disruption in Saccharopolyspora erythraea.

Derivatives of erythromycin with modifications at their C-6 position are generally sought for their increased stability at acid pH, which in turn may confer improved pharmacological properties. A recombinant mutant of the erythromycin-producing bacterium, Saccharopolyspora erythraea, produced an erythromycin derivative, 6-deoxyerythromycin A, that could not be obtained readily by chemical synthesis. This product resulted from targeted disruption of the gene, designated eryF (systematic nomenclature, CYP107), that apparently codes for the cytochrome P450, 6-deoxyerythronolide B (DEB) hydroxylase, which converts DEB to erythronolide B (EB). Enzymes normally acting on EB can process the alternative substrate DEB to form the biologically active erythromycin derivative lacking the C-6 hydroxyl group.

Amino Acid Sequence↗
PubMed1991

Dunaimycins, a new complex of spiroketal 24-membered macrolides with immunosuppressive activity. II. Isolation and elucidation of structures.

A novel complex of antifungal and immunosuppressant compounds has been isolated from the fermentation broth and mycelia of two strains of Streptomyces diastatochromogenes. The structures of eight related components were determined employing 1D and 2D homonuclear and the heteronuclear NMR spectroscopy and mass spectrometry. These structures represent the first reported spiroketal 24-membered macrolide natural products related to the common 26-membered oligomycins.

Anti-Bacterial Agents↗
PubMed1990

Altromycins, novel pluramycin-like antibiotics. II. Isolation and elucidation of structure.

A novel complex of Gram-positive antibiotics was produced from the fermentation of an actinomycete culture AB 1246E-26. The antibiotics were recovered from the whole fermentation broth by extraction with organic solvent and isolated using counter-current chromatography. UV and IR data place these compounds in the anthraquinone-derived class of antibiotics. Mass spectral and NMR data indicate a new complex of compounds related to, but distinctly different from the pluramycin type antibiotics.

Aminoglycosides↗
PubMed1989

Pacidamycins, a novel series of antibiotics with anti-Pseudomonas aeruginosa activity. II. Isolation and structural elucidation.

A novel class of antibiotics was isolated from cultures of Streptomyces coeruleorubidus strain AB 1183F-64. The antimicrobial activity of the pacidamycins is selective against Pseudomonas aeruginosa. The various congeners are nucleoside peptides which differ in the terminal amino acid residues. The structures were determined using MS-MS and 2D NMR techniques.

Anti-Bacterial Agents↗
PubMed1988

Phenelfamycins, a novel complex of elfamycin-type antibiotics. II. Isolation and structure determination.

A novel complex of elfamycin-type antibiotics has been isolated from submerged fermentation of either Streptomyces violaceoniger AB 999F-80 or Streptomyces violaceoniger AB 1047T-33. Antibiotics were extracted from the fermentation broth with ethyl acetate and from the mycelia with acetone. Purification of individual components was achieved by a combination of solvent partitions, Sephadex LH-20 exclusion, C18 bonded-phase silica gel adsorption, diol partition and liquid-liquid countercurrent chromatographies. Seven closely related components were separated and assigned structures 4, 11, 12, 13, 14, and 16 to phenelfamycins A to F respectively and structure 17 to unphenelfamycin. These structures were elucidated employing a variety of spectroscopic techniques, including extensive use of 1D and 2D NMR spectroscopy.

Aminoglycosides↗
PubMed1987

Coloradocin, an antibiotic from a new Actinoplanes. II. Identity with luminamicin and elucidation of structure.

Coloradocin was isolated from a fermentation broth by adsorption onto Amberlite XAD-2. The activity was eluted in MeOH and purified by gel filtration on Shephadex LH-20, followed by liquid-liquid chromatography on diol-bonded silica gel. The last two steps in the purification of this antibiotic included reverse-phase chromatography on C18-bonded silica gel and countercurrent chromatography on an Ito Coil Planet Centrifuge to give material of 90% purity. Analytically pure material was obtained by preparative HPLC. As a result of extensive homo and heteronuclear two-dimensional NMR studies, a structure was proposed for coloradocin. The structure consists of a decalin ring system fused to a 10-membered macrolactone which in turn is fused to a 14-membered macrolactone possessing an enol ether in conjugation with an unsaturated cyclic anhydride functionality. Coloradocin is related to a small class of antibiotics which include nodusmicin and nargenicin and was shown to be identical to luminamicin for which no structure has been reported.

Anti-Bacterial Agents↗