Gausemycins A,B – Cyclic Lipoglycopeptides from Streptomyces Sp.

2020 ◽  
Author(s):  
Anton Tyurin ◽  
Vera Alferova ◽  
Alexander Paramonov ◽  
Maxim Shuvalov ◽  
Gulnara Kudryakova ◽  
...  
Keyword(s):  
Cyclic Peptides ◽  
Pore Formation ◽  
Structural Features ◽  
Side Chain ◽  
Peptide Antibiotic ◽  
Streptomyces Sp ◽  
Gram Positive Bacteria ◽  
Low Concentrations ◽  
Phenylbutyric Acid ◽  
Peptide Core

We report a novel family of natural lipoglycopeptides produced by Streptomyces sp. INA-Ac-5812. Two major components of the mixture, named gausemycins A and B, were isolated, and their structures were elucidated. The compounds are cyclic peptides with a unique peptide core and several remarkable structural features, including unusual positions of D-amino acids, lack of the Ca2+ -binding Asp-X-Asp-Gly (DXDG) motif, tyrosine glycosylation with arabinose, presence of 2-amino-4-hydroxy-4- phenylbutyric acid (Ahpb) and chlorinated kynurenine (ClKyn), N-acylation of the ornithine side chain. These major components of the peptide antibiotic family have pronounced activity against Gram-positive bacteria. The mechanism of action of gausemycins was explored by a number of methods, showing significant differences compared to glycopeptides and related lipopeptides. For example, gausemycins exhibit no Ca2+ -dependence of antimicrobial activity and induce no pore formation at low concentrations. Moreover, there is no detectable accumulation of cell wall biosynthesis precursors under treatment with gausemycins.

scholarly journals Gausemycins A,B – Cyclic Lipoglycopeptides from Streptomyces Sp.

2020 ◽  
Author(s):  
Anton Tyurin ◽  
Vera Alferova ◽  
Alexander Paramonov ◽  
Maxim Shuvalov ◽  
Gulnara Kudryakova ◽  
...  
Keyword(s):  
Cyclic Peptides ◽  
Pore Formation ◽  
Structural Features ◽  
Side Chain ◽  
Peptide Antibiotic ◽  
Streptomyces Sp ◽  
Gram Positive Bacteria ◽  
Low Concentrations ◽  
Phenylbutyric Acid ◽  
Peptide Core

We report a novel family of natural lipoglycopeptides produced by Streptomyces sp. INA-Ac-5812. Two major components of the mixture, named gausemycins A and B, were isolated, and their structures were elucidated. The compounds are cyclic peptides with a unique peptide core and several remarkable structural features, including unusual positions of D-amino acids, lack of the Ca2+ -binding Asp-X-Asp-Gly (DXDG) motif, tyrosine glycosylation with arabinose, presence of 2-amino-4-hydroxy-4- phenylbutyric acid (Ahpb) and chlorinated kynurenine (ClKyn), N-acylation of the ornithine side chain. These major components of the peptide antibiotic family have pronounced activity against Gram-positive bacteria. The mechanism of action of gausemycins was explored by a number of methods, showing significant differences compared to glycopeptides and related lipopeptides. For example, gausemycins exhibit no Ca2+ -dependence of antimicrobial activity and induce no pore formation at low concentrations. Moreover, there is no detectable accumulation of cell wall biosynthesis precursors under treatment with gausemycins.

scholarly journals Gausemycins A,B – Cyclic Lipoglycopeptides from Streptomyces Sp.

2021 ◽  
Author(s):  
Anton Tyurin ◽  
Vera Alferova ◽  
Alexander Paramonov ◽  
Maxim Shuvalov ◽  
Gulnara Kudryakova ◽  
...  
Keyword(s):  
Cyclic Peptides ◽  
Pore Formation ◽  
Structural Features ◽  
Side Chain ◽  
Cell Wall Biosynthesis ◽  
Peptide Antibiotic ◽  
Gram Positive Bacteria ◽  
Low Concentrations ◽  
Phenylbutyric Acid ◽  
Peptide Core

We report a novel family of natural lipoglycopeptides produced by <i>Streptomyces</i> sp. INA-Ac-5812. Two major components of the mixture, named gausemycins A and B, were isolated, and their structures were elucidated. The com-pounds are cyclic peptides with a unique peptide core and several remarkable structural features, including unusual posi-tions of D-amino acids, lack of the Ca<sup>2+</sup>-binding Asp-X-Asp-Gly (DXDG) motif, tyrosine glycosylation with arabinose, presence of 2-amino-4-hydroxy-4-phenylbutyric acid (Ahpb) and chlorinated kynurenine (ClKyn), N-acylation of the or-nithine side chain. These major components of the peptide antibiotic family have pronounced activity against Gram-positive bacteria. The mechanism of action of gausemycins was explored by a number of methods, showing significant differences compared to glycopeptides and related lipopeptides. Gausemycins exhibit only slight Ca<sup>2+</sup>-dependence of an-timicrobial activity and induce no pore formation at low concentrations. Moreover, there is no detectable accumulation of cell wall biosynthesis precursors under treatment with gausemycins.

scholarly journals Cuevaenes C–E: Three new triene carboxylic derivatives from Streptomyces sp. LZ35ΔgdmAI

2014 ◽  
Vol 10 ◽  
pp. 858-862 ◽  
Author(s):  
Jing-Jing Deng ◽  
Chun-Hua Lu ◽  
Yao-Yao Li ◽  
Shan-Ren Li ◽  
Yue-Mao Shen
Keyword(s):  
Spectroscopic Data ◽  
High Resolution Mass Spectrometry ◽  
Fusarium Verticillioides ◽  
Side Chain ◽  
Moderate Activity ◽  
Strain Atcc ◽  
Geometrical Isomers ◽  
Streptomyces Sp ◽  
Gram Positive Bacteria ◽  
Modest Activity

Two pairs of geometrical isomers – cuevaenes A (1) and C (3) as well as cuevaenes D (4) and E (5) – and cuevaene B (2) were isolated from gdmAI-disrupted Streptomyces sp. LZ35. The constitution of cuevaene C (3) was found to be identical to cuevaene A (1) by means of NMR spectroscopy and high resolution mass spectrometry. However, the relative configurations of the triene side chain moieties were determined to be different. It was established on the basis of spectroscopic data that cuevaenes D (4) and E (5) are amides and geometrical isomers. Cuevaenes A–C (1–3) displayed moderate activity against Gram-positive bacteria (e.g., Bacillus subtilis strain ATCC 11060) and modest activity against fungi (e.g., Fusarium verticillioides strain S68 and Rhizoctonia solani strain GXE4). However, cuevaenes D (4) and E (5) showed no inhibitory activity against any of the tested microbes.

Structural features determining the antibiotic potencies of natural and synthetic hop bitter resins, their precursors and derivatives

1975 ◽  
Vol 21 (2) ◽  
pp. 205-212 ◽  
Author(s):  
Arno F. Schmalreck ◽  
M. Teuber ◽  
W. Reininger ◽  
A. Hartl
Keyword(s):  
General Rule ◽  
Structural Features ◽  
Antimicrobial Activities ◽  
Inhibitory Effect ◽  
Ring Structure ◽  
Side Chain ◽  
Gram Positive Bacteria ◽  
Bacillus Subtilis 168 ◽  
Additional Losses ◽  
Active Substances

Twenty-six hop bitter resins, some hitherto not investigated, were tested for antimicrobial activities. Gram-positive bacteria were much more sensitive than Gram-negative ones. The inhibitory effect against Bacillus subtilis 168 was measured by several methods and the general rule could be established that the antibiotic properties are mainly dependent on the hydrophobic parts of the molecules. Thus the acyl-lupuphenones (2-acyl-3, 5-4, 4′, 6-tri(3-methyl-2-butenyl)-cyclohexane-triones (1, 3, 5)) having three prenyl and one acyl side chain are the most active substances. Their minimum inhibitory concentration (MIC) increases from the capro (0.5 μM) to the aceto derivative (11 μM). Any substitution with hydrophilic functions or loss of hydrophobic groups causes reductions in biological activity. This is most evident with the corresponding acyl-phloroglucine precursors (2-acyl-1, 3, 5-trihydroxybenzenes) which lack the three prenyl side chains (MIC, 110 to 5050 μM respectively). Conversion of the central six-membered ring structure into a five-membered one results in additional losses of antimicrobial activity. These findings support the proposal that the lipophilic region of the cell membrane represents the target site for the hop bitter resins.

scholarly journals Unusual Structural Features in the Adduct of Dirhodium Tetraacetate with Lysozyme

2021 ◽  
Vol 22 (3) ◽  
pp. 1496
Author(s):  
Domenico Loreto ◽  
Giarita Ferraro ◽  
Antonello Merlino
Keyword(s):  
Anticancer Agents ◽  
Structural Features ◽  
Side Chain ◽  
Side Chains ◽  
Valuable Insight ◽  
Experimental Conditions ◽  
Egg White Lysozyme ◽  
Potential Applications ◽  
Model Protein ◽  
Hen Egg White

The structures of the adducts formed upon reaction of the cytotoxic paddlewheel dirhodium complex [Rh2(μ-O2CCH3)4] with the model protein hen egg white lysozyme (HEWL) under different experimental conditions are reported. Results indicate that [Rh2(μ-O2CCH3)4] extensively reacts with HEWL:it in part breaks down, at variance with what happens in reactions with other proteins. A Rh center coordinates the side chains of Arg14 and His15. Dimeric Rh–Rh units with Rh–Rh distances between 2.3 and 2.5 Å are bound to the side chains of Asp18, Asp101, Asn93, and Lys96, while a dirhodium unit with a Rh–Rh distance of 3.2–3.4 Å binds the C-terminal carboxylate and the side chain of Lys13 at the interface between two symmetry-related molecules. An additional monometallic fragment binds the side chain of Lys33. These data, which are supported by replicated structural determinations, shed light on the reactivity of dirhodium tetracarboxylates with proteins, providing useful information for the design of new Rh-containing biomaterials with an array of potential applications in the field of catalysis or of medicinal chemistry and valuable insight into the mechanism of action of these potential anticancer agents.

Tylopeptin B peptide antibiotic in lipid membranes at low concentrations: Self-assembling, mutual repulsion and localization

2021 ◽  
pp. 183585
Author(s):  
Victoria N. Syryamina ◽  
Natalia E. Sannikova ◽  
Marta De Zotti ◽  
Marina Gobbo ◽  
Fernando Formaggio ◽  
...  
Keyword(s):  
Lipid Membranes ◽  
Peptide Antibiotic ◽  
Self Assembling ◽  
Low Concentrations

ChemInform Abstract: M10709, a New Cyclic Peptide Antibiotic from Clinically Isolated Streptomyces sp.

ChemInform ◽  
2010 ◽  
Vol 41 (17) ◽  
Author(s):  
Takuya Kumamoto ◽  
Hiroyuki Koshino ◽  
Daisuke Watanabe ◽  
Yuko Matsumoto ◽  
Kazuki Aoyama ◽  
...  
Keyword(s):  
Cyclic Peptide ◽  
Peptide Antibiotic ◽  
Streptomyces Sp

Val-Geninthiocin: Structure Elucidation and MSn Fragmentation of Thiopeptide Antibiotics Produced by Streptomyces sp. RSF18

2008 ◽  
Vol 63 (10) ◽  
pp. 1223-1230 ◽  
Author(s):  
Imran Sajid ◽  
Khaled A. Shaaban ◽  
Holm Frauendorf ◽  
Shahida Hasnain ◽  
Hartmut Laatscha
Keyword(s):  
Amino Acids ◽  
Biological Activity ◽  
Antifungal Activity ◽  
Structure Elucidation ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Unusual Amino Acids ◽  
Streptomyces Sp ◽  
Gram Positive Bacteria ◽  
Thiopeptide Antibiotics

AbstractVal-Geninthiocin (2), a new member of thiopeptide antibiotics, was isolated from the mycelium of Streptomyces sp. RSF18, along with the closely related geninthiocin (1) and the macrolide, chalcomycin. By intensive NMR and MS studies, Val-geninthiocin (2) was identified as desoxygeninthiocin, a thiopeptide, containing several oxazole and thiazole units and a number of unusual amino acids. Compound 2 shows potent activity against Gram-positive bacteria and minor antifungal activity, while it is not effective against Gram-negative bacteria or microalgae. Here we describe the fermentation, isolation and structure elucidation as well as the biological activity of 2.

scholarly journals Structural complexes in the squid giant axon membrane sensitive to ionic concentrations and cardiac glycosides

1976 ◽  
Vol 69 (1) ◽  
pp. 19-28 ◽  
Author(s):  
GM Villegas ◽  
J Villegas
Keyword(s):  
Cardiac Glycosides ◽  
Sea Water ◽  
Giant Axon ◽  
Structural Features ◽  
Nerve Fibers ◽  
Axon Membrane ◽  
Ionic Concentrations ◽  
Low Concentrations ◽  
High Calcium ◽  
Active Ion Transport

Giant nerve fibers of squid Sepioteuthis sepiodea were incubated for 10 min in artificial sea water (ASW) under control conditions, in the absence of various ions, and in the presence of cardiac glycosides. The nerve fibers were fixed in OsO(4) and embedded in Epon, and structural complexes along the axolemma were studied. These complexes consist of a portion of axolemma exhibiting a three-layered substructure, an undercoating of a dense material (approximately 0.1μm in length and approximately 70-170 A in thickness), and a narrowing to disappearance of the axon-Schwann cell interspace. In the controls, the incidence of complexes per 1,000μm of axon perimeter was about 137. This number decreased to 10-25 percent when magnesium was not present in the incubating media, whatever the calcium concentration (88, 44, or 0 mM). In the presence of magnesium, the number and structural features of the complexes were preserved, though the number decreased to 65 percent when high calcium was simultaneously present. The complexes were also modified and decreased to 26-32 percent by incubating the nerves in solutions having low concentrations of sodium and potassium. The adding of 10(-5) M ouabain or strophanthoside to normal ASW incubating solution decreased them to 20-40 percent. Due to their sensitivity to changes in external ionic concentrations and to the presence of cardiac glycosides, the complexes are proposed to represent the structural correlate of specialized sites for active ion transport, although other factors may be involved.

scholarly journals Novel Trifluoromethyl Pyrimidinone Compounds With Activity Against Mycobacterium tuberculosis

2021 ◽  
Vol 9 ◽  
Author(s):  
Erik Hembre ◽  
Julie V. Early ◽  
Joshua Odingo ◽  
Catherine Shelton ◽  
Olena Anoshchenko ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Major Change ◽  
Structural Features ◽  
Research Area ◽  
Biological Properties ◽  
Pyridyl Ring ◽  
Pyridyl Group ◽  
Gram Positive Bacteria ◽  
Wide Range ◽  
Cytotoxic Molecules

The identification and development of new anti-tubercular agents are a priority research area. We identified the trifluoromethyl pyrimidinone series of compounds in a whole-cell screen against Mycobacterium tuberculosis. Fifteen primary hits had minimum inhibitory concentrations (MICs) with good potency IC90 is the concentration at which M. tuberculosis growth is inhibited by 90% (IC90 &lt; 5 μM). We conducted a structure–activity relationship investigation for this series. We designed and synthesized an additional 44 molecules and tested all analogs for activity against M. tuberculosis and cytotoxicity against the HepG2 cell line. Substitution at the 5-position of the pyrimidinone with a wide range of groups, including branched and straight chain alkyl and benzyl groups, resulted in active molecules. Trifluoromethyl was the preferred group at the 6-position, but phenyl and benzyl groups were tolerated. The 2-pyridyl group was required for activity; substitution on the 5-position of the pyridyl ring was tolerated but not on the 6-position. Active molecules from the series demonstrated low selectivity, with cytotoxicity against eukaryotic cells being an issue. However, there were active and non-cytotoxic molecules; the most promising molecule had an MIC (IC90) of 4.9 μM with no cytotoxicity (IC50 &gt; 100 μM). The series was inactive against Gram-negative bacteria but showed good activity against Gram-positive bacteria and yeast. A representative molecule from this series showed rapid concentration-dependent bactericidal activity against replicating M. tuberculosis bacilli with ~4 log kill in &lt;7 days. Overall the biological properties were promising, if cytotoxicity could be reduced. There is scope for further medicinal chemistry optimization to improve the properties without major change in structural features.

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