Archazolid‐7‐<i>O</i>‐β‐<scp>D</scp>‐glucopyranoside – Isolation, Structural Elucidation and Solution Conformation of a Novel V‐ATPase Inhibitor from the Myxobacterium <i>Cystobacter violaceus</i>

Menche, Dirk; Hassfeld, Jorma; Steinmetz, Heinrich; Huss, Markus; Wieczorek, Helmut; Sasse, Florenz

doi:10.1002/ejoc.200600912

Cited by 25 publications

(27 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the course of previous studies 27 the myxobacterium Cystobacter violaceus strain Cb vi105 22 has been identified as an efficient source for structurally novel archazolid derivatives, while Archangium gephyra strain Ar 3548 16 was a more productive source for archazolids A (1) and B (2). In order to study minor natural archazolid derivatives, each of these organisms was cultivated in 350 L bioreactors with 300 L of medium in the presence of Amberlite XAD-16 (1%) for adsorption.…”

Section: ' Results and Discussionmentioning

confidence: 99%

“…19 Very recently, the binding site in this subunit has been analyzed in more detail by cross-linking experiments of an archazolid A derivative in combination with site-directed mutagenesis studies of the protein, demonstrating that archazolid A (1) binds to the equatorial region of the c-ring. 20 While the archazolids were originally isolated from Archangium gephyra, more recent reports have indicated that the myxobacterium Cystobacter violaceus produces a greater diversity of archazolids, and two other derivatives, archazolid C (3) 21 and archazolid D (4), with glucosides at C-7 (3 and 4) and an additional hydroxyl group (4), 22 have been isolated from this myxobacterium. While the archazolids were originally reported as planar structures, their absolute and relative stereochemistry was determined in 2006 by high-field NMR studies in combination with ABSTRACT: Two structurally novel analogues of the macrolides archazolids A and B, archazolid A-15-O-β-D-glucopyranoside (archazolid E, 5) and iso-archazolid B (archazolid F, 6), were isolated from the myxobacterium Cystobacter violaceus and Archangium gephyra, respectively.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Archazolid A-15-O-β-d-glucopyranoside and iso-Archazolid B: Potent V-ATPase Inhibitory Polyketides from the Myxobacteria Cystobacter violaceus and Archangium gephyra

et al. 2011

Self Cite

View full text Add to dashboard Cite

show abstract

Section: ' Results and Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Archazolid A-15-O-β-d-glucopyranoside and iso-Archazolid B: Potent V-ATPase Inhibitory Polyketides from the Myxobacteria Cystobacter violaceus and Archangium gephyra

et al. 2011

Self Cite

View full text Add to dashboard Cite

show abstract

“…6B). In contrast, preincubation with apicularen A, a member of the benzolactone enamides family of V-ATPase inhibitors, which is predicted to have a binding site totally different from archazolid and the plecomacrolides (12,19,32), did not impede the binding of archazolid A as indicated by a clear prevention of NCD-4 labeling (Fig. 6A, lane 9).…”

Section: Labeling Of the V-atpase With A Radioactive Analog Of Archazmentioning

confidence: 93%

Archazolid A Binds to the Equatorial Region of the c-Ring of the Vacuolar H+-ATPase

Bockelmann

Menche

Rudolph

et al. 2010

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

The macrolactone archazolid is a novel, highly specific V-ATPase inhibitor with an IC 50 Vacuolar ATPases (V-ATPases)3 are heteromultimeric proteins that use the energy of ATP hydrolysis to translocate protons from the cytoplasm into intracellular compartments or across the plasma membrane of eukaryotic cells. This transport of protons is mediated by the membrane-integral V O complex, whereas the cleavage of ATP occurs at the cytoplasmatic V 1 complex (1). The V O complex is composed of single copies of subunits a, d, and e, and the ring-forming proteolipid subunits c, cЉ, and in fungi subunit cЈ also (2). Based on the crystal structure from the V O ring of K subunits, a homologue of the H ϩ -translocating subunit c in the V-type Na ϩ -ATPase from Enterococcus hirae, and a cryoelectron microscopy structure from the V-ATPase of Manduca sexta, an arrangement of 10 subunits is proposed for the V O ring (3, 4). The subunits c and cЈ are predicted to have four transmembrane helices (TM 1 to 4), whereas subunit cЉ contains an additional fifth transmembrane helix. All proteolipid subunits contain a conserved glutamate residue, subunits c and cЈ in TM4 and subunit cЉ in TM3, which are essential for proton transport across the membrane (2). This glutamate is a target for the covalent binding inhibitor N,NЈ-dicyclohexylcarbodiimide (DCCD) and its derivatives (5-8).By regulating the pH homeostasis and membrane energization of cells, V-ATPases are involved in a variety of fundamental processes like vesicular trafficking or secondary transport. In addition, plasma membrane V-ATPases are responsible for extracellular acidification, e.g. in osteoclasts or metastasing tumor cells, and therefore play an important role in severe diseases such as osteoporosis or cancer (7). For these reasons the V-ATPase is a promising therapeutic target, and inhibitors of this enzyme are the focus of biomedical research. A variety of such compounds has been discovered of which the plecomacrolide inhibitors bafilomycin and concanamycin are the best studied examples (9). With IC 50 values at low nanomolar concentrations these compounds are highly specific inhibitors of the V-ATPase (10). Throughout the past years the binding site and inhibition mechanism of the plecomacrolides has been studied in more detail. In 2002 Bowman et al. (11) identified via mutagenesis studies in Neurospora crassa amino acids in V O subunit c that contribute to the binding of bafilomycin. In the same year photoaffinity labeling studies with the radioactive concanamycin derivative 125 I-concanolid A also resulted in the *

show abstract

“…The most-potent representatives, archazolid A (1) and B (7) (Scheme 1), only differ in the methylation pattern at C-2; likewise reported glucosides 21,22 are less active by a factor of around 1000.…”

Section: Stereochemical Determinationmentioning

confidence: 97%

Recent Advances in the Stereochemical Determination and Total Synthesis of Myxobacterial Polyketides

Kretschmer¹,

Menche²

2010

Synlett

Self Cite

View full text Add to dashboard Cite

Myxobacteria are a rich source of structurally diverse polyketides with unique architectures. Many of these compounds are associated with high biological activities, including antiproliferative, antibiotic, antifungal, and antiplasmodial activities, and in many cases specific targets are addressed at the molecular level. Unfortunately, many of these compounds were originally only reported as flat structures, impeding further advancement. In recent years, considerable progress has been made on the stereochemical determination and total syntheses of myxobacterial polyketides. This account highlights from a personal perspective illustrative examples of recent advances in the stereochemical determination and total synthesis of myxobacterial polyketides.

show abstract

Archazolid‐7‐O‐β‐D‐glucopyranoside – Isolation, Structural Elucidation and Solution Conformation of a Novel V‐ATPase Inhibitor from the Myxobacterium Cystobacter violaceus

Cited by 25 publications

References 19 publications

Archazolid A-15-O-β-d-glucopyranoside and iso-Archazolid B: Potent V-ATPase Inhibitory Polyketides from the Myxobacteria Cystobacter violaceus and Archangium gephyra

Archazolid A-15-O-β-d-glucopyranoside and iso-Archazolid B: Potent V-ATPase Inhibitory Polyketides from the Myxobacteria Cystobacter violaceus and Archangium gephyra

Archazolid A Binds to the Equatorial Region of the c-Ring of the Vacuolar H+-ATPase

Recent Advances in the Stereochemical Determination and Total Synthesis of Myxobacterial Polyketides

Contact Info

Product

Resources

About