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E Selva

Publications and source records attributed to E Selva.

36 records · Page 2Linked to original sources
PubMed1995

Antibiotic GE37468 A: a novel inhibitor of bacterial protein synthesis. II. Structure elucidation.

GE37468 A is a novel antibiotic produced by Streptomyces sp. ATCC 55365. It has molecular mass 1309.48 and formula C59H52O12N14S5 and belongs to the thiazolyl peptide group of antibiotics. The structure was elucidated by 1H and 13C NMR and MS studies on intact molecule and its hydrolysis products. The antibiotic is a highly modified peptide containing a macrocycle and a side chain composed of a thiazole ring and two dehydroalanine units.

Anti-Bacterial Agents↗
PubMed1995

Antibiotic GE37468 A: a new inhibitor of bacterial protein synthesis. I. Isolation and characterization.

GE37468 A is a new thiazolyl peptide antibiotic obtained by fermentation of Streptomyces sp. strain ATCC 55365. It inhibits bacterial protein synthesis by acting on elongation factor Tu and is structurally and functionally related to the GE2270 class of EF-Tu inhibitors. It is active in vitro against Gram-positive bacteria and Bacteroides fragilis, and protects mice against Staphylococcus aureus infection.

Animals↗
PubMed1993

Mitogen-activated protein kinase stimulation by a tyrosine kinase-negative epidermal growth factor receptor.

Mutation of the epidermal growth factor receptor (EGF-R) within the ATP binding subdomain results in a receptor that lacks tyrosine kinase activity and is defective in signal transduction. However, this kinase-negative EGF-R is able to activate MAP kinase (Campos-Gonzalez, R., and Glenny, J. R. (1992) J. Biol. Chem. 267, 14535-14538). This observation suggests that signal initiation by the EGF-R can occur by a mechanism that is independent of the receptor tyrosine kinase activity. Here, we report that the kinase-negative EGF-R is phosphorylated on tyrosine in EGF-treated cells. The mechanism of tyrosine phosphorylation can be accounted for by the action of EGF to stimulate a protein kinase activity that is associated with the kinase-negative EGF-R. This protein kinase activity is not intrinsic to the receptor and can be separated from the EGF-R by incubation with 0.5 M NaCl. MAP kinase activation by the kinase-negative EGF-R may therefore occur by a mechanism that requires a receptor-associated tyrosine kinase. Thus, it is unnecessary to propose a novel kinase-independent mechanism of signal initiation to account for MAP kinase activation by the kinase-negative EGF-R.

Amino Acid Sequence↗
PubMed1992

Determination of the acyl moieties of the antibiotic complex A40926 and their relation with the membrane lipids of the producer strain.

Structures of the fatty acid residues characterizing the various components of A40926 were determined by gas chromatography/mass spectrometry on the methyl esters obtained by methanolysis of the complex. The results confirm the residues previously assigned to Factor A (n-undecanoic acid) and B (10-methyl-undecanoic acid) and establish the residues of Factor A1 (9-methyl-decanoic acid), B1 (n-dodecanoic acid), RS1 (8-methyl-nonanoic acid), RS2 (n-decanoic acid), and RS3 (n-tridecanoic acid). As the Actinomadura species contain in their mycelia large quantities of C15-C17 fatty acid residues as membrane phospholipids, these mycelia were saponified and the fatty acids obtained were analyzed as above. There is a close correlation between the fatty acid content of A40926 complex and that of the longer homologues in the producer mycelia.

Anti-Bacterial Agents↗
PubMed1991

A high throughput assay for inhibitors of HIV-1 protease. Screening of microbial metabolites.

A novel method for discovery of HIV-1 protease inhibitors in complex biological samples has been developed. The assay is based on two specific reagents: a recombinant protein constituted by a portion of the HIV-1 Gag polyprotein comprising the p17-p24 cleavage site, fused to E. coli beta-galactosidase, and a monoclonal antibody which binds the fusion protein in the Gag region. Binding occurs only if the fusion protein has not been cleaved by the HIV-1 protease. The assay has been adapted for the screening of large numbers of samples in standard 96-well microtiter plates. Using this method about 12000 microbial fermentation broths have been tested and several HIV-1 protease inhibitory activities have been detected. One of these has been studied in detail.

Amino Acid Sequence↗
PubMed1991

Constitutive phosphorylation of the epidermal growth factor receptor blocks mitogenic signal transduction.

The epidermal growth factor (EGF) receptor is phosphorylated by protein kinase C at Thr654. It has been proposed that the phosphorylation of this site is an important regulatory mechanism for the control of EGF receptor function. However, the physiological significance of the phosphorylation of EGF receptor Thr654 in intact cells is not understood. To address this question, the design of an experimental strategy is required that can be used to distinguish between the pleiotropic effects of kinase C activation and the specific effects of kinase C that are mediated by the phosphorylation of the EGF receptor at Thr654. The approach that we used was to examine the function of EGF receptors that are constitutively phosphorylated at residue 654. It was observed that the constitutive phosphorylation of the EGF receptor blocked mitogenic signal transduction by the receptor. These data are consistent with the hypothesis that the phosphorylation of the EGF receptor at residue 654 in intact cells inhibits EGF-stimulated cellular proliferation.

Animals↗
PubMed1991

Antibiotic GE2270 a: a novel inhibitor of bacterial protein synthesis. I. Isolation and characterization.

A novel antibiotic, GE2270 A, was isolated from the fermentation broth of a strain of Planobispora rosea. The product was found to inhibit bacterial protein synthesis. Structural characteristics showed similarities between GE2270 A and thiazolyl peptides such as micrococcin which is known to inhibit protein synthesis by acting directly on the ribosome. Despite this similarity GE2270 A showed functional analogy to kirromycin-like antibiotics and pulvomycin, as its molecular target was found to be elongation factor Tu (EF-Tu). GE2270 A is active against Gram-positive microorganism and anaerobes and differs from the other EF-Tu inhibitors in its spectrum of antimicrobial activity.

Actinomycetales↗
PubMed1991

Antibiotic GE2270 a: a novel inhibitor of bacterial protein synthesis. II. Structure elucidation.

GE2270 A, produced by Planobispora rosea ATCC 53773, inhibits Gram-positive bacteria and anaerobes by acting on the bacterial protein synthesis. The structure has been determined by physico-chemical methods applied to the intact molecule and to the main hydrolysis products. Characterization by UV, IR, NMR (double quantum filter COSY), acid-base ionization, elemental analysis and FAB-MS indicated that GE2270 A is a highly modified peptide having MW 1,289 and formula C56H55N15O10S6, and a weak basic function, and that it belongs to the thiazolyl peptide group of antibiotics. Acid hydrolysis yielded a main product (MW 634), responsible for the chromophoric absorption, and a number of hydrolyzed products of lower MW. 13C NMR inverse techniques and MS studies (EI, positive ion chemical ionization, and collision induced dissociation FAB-MS-MS experiments) on GE2270 A, the chromophoric compound, and the other hydrolysis products led to the complete identification of the various amino acid residues and their sequence. Two out of the six chiral centers have been determined. The structure is thought to originate from modification of a chain of 14 amino acids in a process which creates 6 thiazole rings and one pyridine. The modification process also closes the linear polypeptide to form a cyclic part with an attached side-chain. GE2270 A plausibly has a similar biosynthetic origin to that of other thiazolyl peptide antibiotics such as nosiheptide and micrococcin.

Actinomycetales↗
PubMed1990

Antibiotic SB22484: a novel complex of the aurodox group. I. Taxonomy of the producing organism, isolation of the antibiotics and chemical and biological characterization.

Antibiotic SB22484 is a novel member of the aurodox type antibiotic group produced in submerged-fermentation cultures of Streptomyces sp. NRRL 15496. The antibiotic complex is composed of two pairs of isomers with MW's of 752 and 766. The individual isomers, which were separated by preparative HPLC, equilibrate to a mixture of the isomer pair when left in aqueous solution. In vitro, SB22484 antibiotics strongly inhibited neisseriae and were also active against Streptococci, Ureaplasma urealyticum and Haemophilus influenzae.

Animals↗
PubMed1990

Antibiotic SB22484: a novel complex of the aurodox group. II. Structure elucidation of the four factors.

SB22484, active against Neisseriae gonorrhoeae and Neisseriae meningitidis, is a complex of four factors, designed 1 through 4, which from two pairs of isomers, 1 and 3, and 2 and 4. Factors 1 and 3 account for 65% of the complex, factor 3 being the predominant one. On the basis of the existing and implemented correlations between structure and physico-chemical characteristics (UV and IR spectroscopies, ionization properties, MS as FAB and as negative and positive CI, 1H NMR spectroscopy as 2D COSY and NOESY) in the aurodox field, the complete structures were assigned. Factor 3 can be described as N-[7-[5(R)-[7-[1,2-dihydro-4-hydroxy-1H-2-oxo-3-pyridinyl]-6-methyl- 7-oxo-1(E),3(E),5(E)-heptatrienyl]tetrahydro-3(S),4(R)-dihydrox yfuran-2 (S)-yl]-6(S)-methoxy-5,7(R)-dimethyl-2(E),4(E)-heptadienyl]-alpha (S)-methyl-5(S)-methyltetrahydro-2(S),4(S or R)-dihydroxy-6(S)-[1(E), 3(Z)-pentadienyl]-2H-pyran-2-acetamide. Factor 1 is an epimer of factor 3 with the opposite configuration at the anomeric center. Factors 2 and 4 have an ethyl group instead of the methyl group alpha to the acetamide moiety and are in the same stereochemical relationship as the pair 1 and 3.

Acid-Base Equilibrium↗
PubMed1989

A42867, a novel glycopeptide antibiotic.

A42867 is a new glycopeptide antibiotic of the ristocetin-vancomycin class active against aerobic and anaerobic Gram-positive bacteria. A42867 is produced by a strain of Nocardia nov. sp. ATCC 53492. A42867 was isolated during a screening program aimed at the discovery of new members of this glycopeptide class of antibiotics, by affinity chromatography based on an acyl-D-alanyl-D-alanine probe. The structure of A42867 was elucidated by fast atom bombardment MS, high field 2D 1H NMR spectroscopy, and HPLC analysis of the hydrolyzed carbohydrates. A42867 differs from vancomycin in the sugar portion and in the presence of only one chlorine atom in the peptide core. Its biological activity on Gram-positive aerobic and anaerobic bacteria is similar to that of other antibiotics of this group.

Aminoglycosides↗
PubMed1988

A40926 aglycone and pseudoaglycones: preparation and biological activity.

A40926 antibiotics are new glycopeptides which are much more active than other members of this class against Neisseria gonorrhoeae. Their activity against Gram-positive bacteria, including coagulase-negative Staphylococci, is similar to that of other glycopeptides. An A40926 preparation containing factors A and B ("A40926 A + B complex") was hydrolyzed to the aglycone and to the mannosyl and N-acylaminoglucuronyl aglycones. The mannosyl aglycone and the aglycone were less active than A40926 A + B complex against Streptococci and Gram-positive anaerobes and lost the anti-gonorrheal activity. In contrast, the N-acylaminoglucuronyl aglycones were as active as the parent complex against these Gram-positive bacteria and were moderately active against N. gonorrhoeae. The aglycone and, even more so, the N-acylaminoglucuronyl aglycones, had better activity than the parent complex against coagulase-negative Staphylococci. In experimental septicemia in the mouse, A40926 A + B complex and its derivatives had activity proportional to their MIC for the test organism.

Animals↗
PubMed1987

A40926, a new glycopeptide antibiotic with anti-Neisseria activity.

In the course of a search for glycopeptide antibiotics having novel biological properties, we isolated A40926. Produced by an actinomycete of the genus Actinomadura, A40926 is a complex of four main factors which contain a fatty acid as part of a glycolipid attached to the peptide backbone. Its activity was, in most respects, similar to that of other glycopeptides, such as vancomycin and teicoplanin. However, in addition to inhibiting gram-positive bacteria, A40926 was very active against Neisseria gonorrhoeae. A40926 was rapidly bactericidal for N. gonorrhoeae clinical isolates at concentrations equal to or slightly higher than the MIC. In mice, levels in serum were higher and more prolonged than those of an equivalent subcutaneous dose of teicoplanin. These properties suggest that A40926 may have potential in the therapy of gonorrhea.

Anti-Bacterial Agents↗
PubMed1984

A-16686, a new antibiotic from Actinoplanes. I. Fermentation, isolation and preliminary physico-chemical characteristics.

Actinoplanes sp. ATCC 33076 is a new strain that was found to produce an antibiotic, designated A-16686, which is a complex of three closely-related polypeptides containing chlorinated phenyl moieties and D-mannose. Both the complex and the single fractions possess a good activity against Gram-positive bacteria. A-16686 specifically inhibits the synthesis of the bacterial cell wall.

Actinomycetales↗