Lapstatin, a new aminopeptidase inhibitor produced by Streptomyces rimosus , inhibits autogenous aminopeptidases

Lampret, Borut; Kidrič, J.; Kralj, Bogdan; Vitale, Ljubinka; Pokorný, Miroslav; Renko, M.

doi:10.1007/s002030050726

Cited by 20 publications

(6 citation statements)

References 31 publications

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“…We therefore speculate that the substitution status of the C3 on the acyl chain of the N-AHSL may affect the degradation rate in situ, to a certain extent. This speculation is in agreement with the observation that an aminopeptidase from Streptomyces rimosus is inhibited by a dipeptide analogue with hydroxy-and amino-substitutions close to the amide bond (Repic Lampret et al, 1999). In relation to this question, the ability of a root-associated micro-organism to degrade the QS signal may indeed constitute a trait conferring a selective advantage to this micro-organism, over other bacterial cells living in the rhizosphere.…”

Section: Discussionsupporting

confidence: 83%

Novel bacteria degrading N-acylhomoserine lactones and their use as quenchers of quorum-sensing-regulated functions of plant-pathogenic bacteria

et al. 2003

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Bacteria degrading the quorum-sensing (QS) signal molecule N-hexanoylhomoserine lactone were isolated from a tobacco rhizosphere. Twenty-five isolates degrading this homoserine lactone fell into six groups according to their genomic REP-PCR and rrs PCR-RFLP profiles. Representative strains from each group were identified as members of the genera Pseudomonas, Comamonas, Variovorax and Rhodococcus. All these isolates degraded N-acylhomoserine lactones other than the hexanoic acid derivative, albeit with different specificity and kinetics. One of these isolates, Rhodococcus erythropolis strain W2, was used to quench QS-regulated functions of other microbes. In vitro, W2 strongly interfered with violacein production by Chromobacterium violaceum, and transfer of pathogenicity in Agrobacterium tumefaciens. In planta, R. erythropolis W2 markedly reduced the pathogenicity of Pectobacterium carotovorum subsp. carotovorum in potato tubers. These series of results reveal the diversity of the QSinterfering bacteria in the rhizosphere and demonstrate the validity of targeting QS signal molecules to control pathogens with natural bacterial isolates.

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Section: Discussionsupporting

confidence: 83%

Novel bacteria degrading N-acylhomoserine lactones and their use as quenchers of quorum-sensing-regulated functions of plant-pathogenic bacteria

et al. 2003

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“…Amastatin, Phebestin, Lapstatin, etc. are also acting as natural small molecule APN inhibitors [1,[28][29][30].…”

Section: Introductionmentioning

confidence: 99%

Exploring the structural aspects of ureido-amino acid-based APN inhibitors: a validated comparative multi-QSAR modelling study

Banerjee

Amin

Baidya

et al. 2020

SAR and QSAR in Environmental Research

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The zinc-dependent enzyme aminopeptidase N (APN) is a member of the M1 metalloenzyme family. The multi-functionality of APN as a peptidase, a receptor and a signalling molecule has provided it the access to influence a number of disease conditions namely viral diseases, angiogenesis, cellular metastasis and invasion including different cancer conditions. Hence, the development of potent APN inhibitors is a possible route for the treatment of diseases related to the activity of APN. In this study, different QSAR approaches have been adopted to identify the structural features of a group of hydroxamate-based ureido-amino acid derivative APN inhibitors. This study was able to identify different constitutional aspects of these APN inhibitors which are important for their inhibitory potency. Additionally, some of these observations were also aligned with the observations of previously performed QSAR studies conducted on different APN inhibitors. Therefore, the results of this study may help to design potent and effective APN inhibitors in the future. ARTICLE HISTORY

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“…Inhibitors with similar binding mode mainly includes: (1) modified or reformed compounds based on Bestatin, e.g. α-Thiobestatin (K i : 4.4 μmol/L), Bestatin thioamide (K i : 40.3 μmol/L) [29] , Lapstatin (IC50: 203 μmol/L) [30] , and para-hydroxybestatin, etc. (Figure 19, 33-35); (2) AHPA derivatives, e.g.…”

Section: Aminopeptidase N (Apn/cd13)mentioning

confidence: 99%

Peptidomimetics and metalloprotease inhibitors as anticancer drugs

2009

Sci. China Ser. B-Chem.

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Peptidomimetics with three types, as the structural or functional mimetics of natural active peptides, can preserve the bioactivity and improve the bioavailability and the specificity towards the targets of the lead peptides. Peptidomimetics of high bioactivity can be designed through various ways including conformation restriction, modification and non-peptide design. Recently the concentration on the development of cancer chemotherapeutic drugs was transferred from cytotoxic drugs to target-based drugs, and many proteases and peptidases that play key roles in the process of tumor genesis and development was discovered, which means that peptidomimetics as potential cancer chemotherapeutic drugs should be paid close attention to. Our laboratory has focused on the development of smallmolecule peptidomimetic inhibitors of APN, MMPs and HDACs as target-based anticancer agents. These three zinc-dependent metalloproteinases play very important roles in the process of tumor genesis, invasion, metastasis, angiogenesis and matrix degradation, so small-molecule peptidomimetic inhibitors based on them would be quite potential in the development of chemotherapeutic drugs with high selectivity.peptidomimetics, drug design, metalloproteinase inhibitors, anticancer agents

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Lapstatin, a new aminopeptidase inhibitor produced by Streptomyces rimosus , inhibits autogenous aminopeptidases

Cited by 20 publications

References 31 publications

Novel bacteria degrading N-acylhomoserine lactones and their use as quenchers of quorum-sensing-regulated functions of plant-pathogenic bacteria

Novel bacteria degrading N-acylhomoserine lactones and their use as quenchers of quorum-sensing-regulated functions of plant-pathogenic bacteria

Exploring the structural aspects of ureido-amino acid-based APN inhibitors: a validated comparative multi-QSAR modelling study

Peptidomimetics and metalloprotease inhibitors as anticancer drugs

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