A New Depsipeptide Antibiotic, Citropeptin

Hayakawa, Yoichi; Nakagawa, Masaya; Toda, Yoichiro; Seto, Haruo

doi:10.1080/00021369.1990.10870082

Cited by 5 publications

(5 citation statements)

References 3 publications

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“…GE3 is a cyclohexadepsipeptide similar to azinothricin [70], citropeptin [71], A83586C [72], variapeptin [73], Lsynthetic standards. The stereochemistry of the piperazic acids and the N-methylleucine were assigned based on similarity to the other cyclohexadepsipeptides.…”

Section: Papuamidesmentioning

confidence: 99%

Recent Developments in Depsipeptide Research

Ballard¹,

Yu²,

Wang³

2002

CMC

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This review focuses on the major developments in depsipeptide research since 1995. Depsipeptides are bio-oligomers composed of hydroxy and amino acids linked by amide and ester bonds. Many depsipeptides show very promising biological activities, including anticancer, antibacterial, antiviral, antifungal, anti-inflammatory, and anti-clotting or anti-antherogenic properties. In this report depsipeptides exhibiting these properties are discussed. Their isolation, structural determination, and notable structural features are discussed, but their biological properties and therapeutic potentials are emphasized. Depsipeptides have shown the greatest therapeutic potential as anticancer agents. Four depsipeptides have entered clinical trials for cancer treatment. Among the antiviral compounds discovered, the callipeltins and the quinoxapeptins are particularly promising due to their inhibitory activities against HIV. These compounds have the potential to be developed as anti-AIDS drugs or to serve as lead compounds for the discovery of structurally related anti-AIDS compounds. Antifungal compounds, such as the jaspamides, may lead to therapies against many of the opportunistic infections that accompany AIDS. Anti-inflammatory compounds such as SCH217048 act as neurokinin antagonists and may lead to anti-inflammatory treatments. Some depsipeptides such as micropeptins and A90720A have been found to be effective plasmin inhibitors, which have implications as treatments for cardiovascular diseases. Compounds such as SCH58149 help control the levels of HDL and LDL.

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Section: Papuamidesmentioning

confidence: 99%

Recent Developments in Depsipeptide Research

Ballard¹,

Yu²,

Wang³

2002

CMC

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“…The structure and use of KRN5500 have been described [3,11]; however, the mechanism by which the drug produces its putative robust effects is unknown. There are two aspects of its effects in both the single human patient and in the animal pain models that speak to possible mechanisms of action.…”

Section: Discussionmentioning

confidence: 99%

“…He was enrolled into a trial of a novel drug, KRN5500, that was being conducted at the MGH Cancer Center for patients with adenocarcinoma of the colon. KRN5500 is a spicamycin derivative [3]. He received six treatment cycles during which 0.8 mg/m 2 /day of KRN5500 was infused for five consecutive days.…”

mentioning

confidence: 99%

Antineuropathic Effects of the Antibiotic Derivative Spicamycin KRN5500

Borsook¹,

Edwards

2004

Pain Med

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Excellence in neuropathic pain management continues to challenge the ability of health care providers. Current medications are helpful but often create significant side effects or simply fail to provide adequate analgesia. We report here on a serendipitous finding of the successful attenuation of neuropathic pain in a patient with long-standing monoclonal gammopathy, Raynaud's disease, and neuropathic pain who received the trial chemotherapeutic agent KRN5500. This finding led to animal studies that have provided support for the possible use of KRN5500 in the treatment of neuropathic pain in humans as well as some insight into the possible mechanism(s) of action of this drug.

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“…These molecules belong to the azinothricin family that consists of cyclic hexadepsipeptides (Figure ). These hexadepsipeptides are biosynthesized by a nonribosomal peptide synthetase (NRPS) system, which starts synthesis of the core peptide after the polyketide synthase (PKS)-derived acyl side chain has been attached to the first amino acid residue. , For the various members of this cyclic peptide class, many different bioactivities such as apoptosis-inducing activity (polyoxypeptins A and B), antitumor activity (diperamycin, citropeptin, and kettapeptin), and activity against Gram-positive bacteria (IC101, diperamycin, variapeptin, aurantimycin, kettapeptin, azinothricin, and A83586C) were reported. Among these substances, only the PKS-NRPS hybrid BGCs of polyoxypeptin and aurantimycin have been described so far. , The antibacterial target is not described; however it was reported that a multidrug resistance ABC transporter is mediating aurantimycin A resistance .…”

mentioning

confidence: 99%

Genome-Mining-Guided Discovery and Characterization of the PKS-NRPS-Hybrid Polyoxyperuin Produced by a Marine-Derived Streptomycete

et al. 2022

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The azinothricin family comprises several cyclic hexadepsipeptides with diverse pharmacological bioactivities, including antimicrobial, antitumoral, and apoptosis induction. In this work, using a genome mining approach, a biosynthetic gene cluster encoding an azinothricin-like compound was identified from the Streptomyces sp. s120 genome sequence (pop BGC). Comparative MS analysis of extracts from the native producer and a knockout mutant led to the identification of metabolites corresponding to the pop BGC. Furthermore, regulatory elements of the BGC were identified. By overexpression of an LmbU-like transcriptional activator, the production yield of 1 and 2 was increased, enabling isolation and structure elucidation of polyoxyperuin A seco acid (1) and polyoxyperuin A (2) using high-resolution mass spectrometry and NMR spectroscopy. Compound 1 exhibited a low antibiotic effect against Micrococcus luteus, while 2 showed a strong Gram-positive antibiotic effect in a micro-broth-dilution assay.

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A New Depsipeptide Antibiotic, Citropeptin

Cited by 5 publications

References 3 publications

Recent Developments in Depsipeptide Research

Recent Developments in Depsipeptide Research

Antineuropathic Effects of the Antibiotic Derivative Spicamycin KRN5500

Genome-Mining-Guided Discovery and Characterization of the PKS-NRPS-Hybrid Polyoxyperuin Produced by a Marine-Derived Streptomycete

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