Bottromycin. Separation of Biologically Active Compounds and Preparation and Testing of Amide Derivatives

Miller, Wolfgang J.; Chaiet, Louis; Rasmussen, G. K.; Christensen, Bert E.; J, Hannah; Ak, Miller; Fj, Wolf

doi:10.1021/jm00310a603

Cited by 10 publications

(8 citation statements)

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“…657 The proposed structure of bottromycin underwent several revisions. Initially proposed to be a linear peptide, 658–660 the major bioactive component bottromycin A 2 was later determined to contain several non-proteinogenic amino acids and a macroamidine. 661 On the basis of 15 N-NMR, the macrocycle vertex was determined to be located in between two t- butyl-containing amino acids, consistent with condensation between the N-terminus and a backbone amide carbonyl.…”

Section: Non-canonical Ycaosmentioning

confidence: 99%

“…Amide derivatives of bottromycin B/C outperformed ester analogs in assays against S. aureus in vivo , while esters tended to be more active than amides in vitro , suggesting a possible difference in pharmacokinetic properties. 660 Indeed, upon addition of bottromycin A 2 in mouse plasma, rapid degradation of the side chain ester to acid was observed (compared to a chemically hydrolyzed standard), and hypothesized to contribute to the poor antimicrobial efficacy. 670 Additional amide, thioester, and ketone derivatives of bottromycin A 2 at this position recapitulated these trends: the thioester analogs showed the lowest plasma stability, but most potent MIC values.…”

Section: Non-canonical Ycaosmentioning

confidence: 99%

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YcaO-Dependent Posttranslational Amide Activation: Biosynthesis, Structure, and Function

et al. 2017

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With advances in sequencing technology, uncharacterized proteins and domains of unknown function (DUFs) are rapidly accumulating in sequence databases and offer an opportunity to discover new protein chemistry and reaction mechanisms. The focus of this review, the formerly enigmatic YcaO superfamily (DUF181), has been found to catalyze a unique phosphorylation of a ribosomal peptide backbone amide upon attack by different nucleophiles. Established nucleophiles are the side chains of Cys, Ser, and Thr which gives rise to azoline/azole biosynthesis in ribosomally synthesized and posttranslationally modified peptide (RiPP) natural products. However, much remains unknown about the potential for YcaO proteins to collaborate with other nucleophiles. Recent work suggests potential in forming thioamides, macroamidines, and possibly additional post-translational modifications. This review covers all knowledge through mid-2016 regarding the biosynthetic gene clusters (BGCs), natural products, functions, mechanisms, and applications of YcaO proteins and outlines likely future research directions for this protein superfamily.

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Section: Non-canonical Ycaosmentioning

confidence: 99%

Section: Non-canonical Ycaosmentioning

confidence: 99%

YcaO-Dependent Posttranslational Amide Activation: Biosynthesis, Structure, and Function

et al. 2017

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“…aureus. [59] Most compounds were active, but the primary and secondary amides were less active than the esters in vitro, but more active in vivo. Similar observations were made with the Weinreb amides of the AiCuris team.…”

Section: Sar Studies Of Bottromycins and Derivativesmentioning

confidence: 98%

“…aureus in mice than the natural product. [59] Researcher at AiCuris used this approach for the synthesis of "Weinrebamide"-type amides by reaction with linear or cyclic N,Odialkylhydroxylamines. [60] The groups of Ōmura and Sunazuka synthesized a range of different derivatives via the correspond- ing hydrazide 103 as common intermediate (Scheme 33).…”

Section: Total Syntheses Of Bottromycin and Analogousmentioning

confidence: 99%

The Long, Long Way to Bottromycin

Kazmaier

2020

Israel Journal of Chemistry

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Although discovered already in the middle of last century, the bottromycins are a unique class of natural products, and a real challenge for all kind of researchers trying to get familiar with them. The structure elucidation was a tour de force and last over 50 years. Synthetic approaches were also painful and it was actually the first and so far only synthesis which confirmed/revised the previously proposed structures. Recent investigations on the biosynthetic pathway indicate that the bottromycins belong to the ribosomally synthesized and posttranslational modified peptides, but that also the biosynthesis does not proceed along the "usual way". This review will cover the development of bottromycin research from the beginning until today, with a focus on synthetic studies, total synthesis and modifications.

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“…two other components of the bottromycin complex, bottromycins B2 and C23, 5,8), to be reinvestigated. For this purpose, I have carried out the unequivocal NMR assignments of all the protons and carbons of bottromycin A2 (1), which is the main component and whose sample is abundantly available.…”

mentioning

confidence: 99%

Studies on Bottromycins. II. Structure Elucidation of Bottromycins B2 and C2.

Kaneda¹

2002

J. Antibiot.

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Bottromycin. Separation of Biologically Active Compounds and Preparation and Testing of Amide Derivatives

Cited by 10 publications

References 1 publication

YcaO-Dependent Posttranslational Amide Activation: Biosynthesis, Structure, and Function

YcaO-Dependent Posttranslational Amide Activation: Biosynthesis, Structure, and Function

The Long, Long Way to Bottromycin

Studies on Bottromycins. II. Structure Elucidation of Bottromycins B2 and C2.

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