A marine natural product, patellamide D, reverses multidrug resistance in a human leukemic cell line

Williams, Allen B.; Jacobs, Robert S.

doi:10.1016/0304-3835(93)90103-g

Cited by 95 publications

(72 citation statements)

References 16 publications

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“…The patellamides display a variety of biological activities including cytotoxicity 2 and as selective antagonists for reversing the multidrug resistant CEM/VLB100 human leukemic cell line towards vinblastine, colchicine and adriamycin treatment. 3 The patellamides are part of a family of bioactive thiazole, thiazoline, oxazole and oxazoline containing natural products including bleomycin, thiostrepton and diazonamide A. 4 The biological activities of this family of alkaloids can be attributed to the conformational constraints imposed by the heterocycles and their ability to bind metals or intercalate into DNA.…”

Section: Introductionmentioning

confidence: 99%

Spontaneity in the patellamide biosynthetic pathway

et al. 2006

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Post-translationally modified ribosomal peptides are unusual natural products and many have potent biological activity. The biosynthetic processes involved in their formation have been delineated for some, but the patellamides represent a unique group of these metabolites with a combination of a macrocycle, small heterocycles and D-stereocentres. The genes encoding for the patellamides show very low homology to known biosynthetic genes and there appear to be no explicit genes for the macrocyclisation and epimerisation steps. Using a combination of literature data and large-scale molecular dynamics calculations with explicit solvent, we propose that the macrocyclisation and epimerisation steps are spontaneous and interdependent and a feature of the structure of the linear peptide. Our study suggests the steps in the biosynthetic route are heterocyclisation, macrocyclisation, followed by epimerisation and finally dehydrogenation. This study is presented as testable hypothesis based on literature and theoretical data to be verified by future detailed experimental investigations.

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Section: Introductionmentioning

confidence: 99%

Spontaneity in the patellamide biosynthetic pathway

et al. 2006

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“…1). Both groups have clinical potential, because patellamides are typically moderately cytotoxic, and patellamides B, C, and D reportedly reverse multidrug resistance (15,16), whereas trunkamide was initially isolated because of specific and unusual activity against the multidrug-resistant UO-31 renal cell line (17). Patellamides are characteristically composed of pseudosymmetrical, cyclic dimers, with each substructure having the sequence thiazolenonpolar amino acid-oxazoline-nonpolar amino acid.…”

mentioning

confidence: 99%

Patellamide A and C biosynthesis by a microcin-like pathway inProchloron didemni, the cyanobacterial symbiont ofLissoclinum patella

Schmidt

Nelson

Rasko

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

552

717

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Prochloron spp. are obligate cyanobacterial symbionts of many didemnid family ascidians. It has been proposed that the cyclic peptides of the patellamide class found in didemnid extracts are synthesized by Prochloron spp., but studies in which host and symbiont cells are separated and chemically analyzed to identify the biosynthetic source have yielded inconclusive results. As part of the Prochloron didemni sequencing project, we identified patellamide biosynthetic genes and confirmed their function by heterologous expression of the whole pathway in Escherichia coli. The primary sequence of patellamides A and C is encoded on a single ORF that resembles a precursor peptide. We propose that this prepatellamide is heterocyclized to form thiazole and oxazoline rings, and the peptide is cleaved to yield the two cyclic patellamides, A and C. This work represents the full sequencing and functional expression of a marine natural-product pathway from an obligate symbiont. In addition, a related cluster was identified in Trichodesmium erythraeum IMS101, an important bloom-forming cyanobacterium.heterocycle ͉ tunicate ͉ ascidian ͉ genome sequencing ͉ lantibiotic

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“…Mussels transplanted from a unpolluted site to a polluted site for 3 days induce their MXR and behave like mussels living at a polluted site (48 (58), or through structure-based selection (59). MDR-inhibiting properties of substances were frequently discovered in a programs initiated to identify MDR-circumventing agents among, for example, many different strains of blue-green algae, or thousands of fungi and Actinomycetes, or a variety of marine species, like tolyporphin (60), or two naphto-g-pyrones (61), or patellamide (62), respectively. Most of these compounds act by increasing the intracellular concentration of cytotoxic drugs probably through direct interaction with the P-glycoprotein.…”

Section: Mxr In Aquatic Organismsmentioning

confidence: 99%

A New Type of Hazardous Chemical: The Chemosensitizers of Multixenobiotic Resistance

Kurelec¹

1997

Environmental Health Perspectives

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A marine natural product, patellamide D, reverses multidrug resistance in a human leukemic cell line

Cited by 95 publications

References 16 publications

Spontaneity in the patellamide biosynthetic pathway

Spontaneity in the patellamide biosynthetic pathway

Patellamide A and C biosynthesis by a microcin-like pathway inProchloron didemni, the cyanobacterial symbiont ofLissoclinum patella

A New Type of Hazardous Chemical: The Chemosensitizers of Multixenobiotic Resistance

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