A facile route has been established for the synthesis of indole-substituted (S)-tryptophans from corresponding indoles, which utilizes a chiral auxiliary-facilitated Strecker amino acid synthesis strategy. The chiral auxiliary reagents evaluated were (S)-methylbenzylamine and related derivatives. To illustrate the robustness of the method, eight optically pure (S)-tryptophan analogues were synthesized, which were subsequently used for the convergent synthesis of a potent antibacterial agent, argyrin A and its analogues.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1039/c4ob02107j | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The cyclic octapeptide antibiotic argyrin B inhibits translation by trapping EF-G on the ribosome during translocation.
Proc Natl Acad Sci U S A
May 2022
Institute for Biochemistry and Molecular Biology, University of Hamburg, 20146 Hamburg, Germany.
Argyrins are a family of naturally produced octapeptides that display promising antimicrobial activity against Pseudomonas aeruginosa. Argyrin B (ArgB) has been shown to interact with an elongated form of the translation elongation factor G (EF-G), leading to the suggestion that argyrins inhibit protein synthesis by interfering with EF-G binding to the ribosome. Here, using a combination of cryo-electron microscopy (cryo-EM) and single-molecule fluorescence resonance energy transfer (smFRET), we demonstrate that rather than interfering with ribosome binding, ArgB rapidly and specifically binds EF-G on the ribosome to inhibit intermediate steps of the translocation mechanism.
View Article and Find Full Text PDFPainting argyrins blue: Negishi cross-coupling for synthesis of deep-blue tryptophan analogue β-(1-azulenyl)-l alanine and its incorporation into argyrin C.
Bioorg Med Chem
October 2018
Institute for Organic Chemistry, Leibniz University Hannover, Schneiderberg 1B, 30167 Hannover and Centre of Biomolecular Drug Research (BMWZ), Schneiderberg 38, 30167 Hannover, Germany; Helmholtz Centre for Infection Research GmbH (HZI), Inhoffenstraße 7, 38124 Braunschweig, Germany. Electronic address:
The argyrins are a family of non-ribosomal peptides that exhibits different biological activities through only small structural changes. Ideally, a biologically active molecule can be tracked and observed in a variety of biological and clinical settings in a non-invasive manner. As a step towards this goal, we report here a chemical synthesis of unnatural deep blue amino acid β-(1-azulenyl)-l alanine with different fluorescence and photophysical properties, which allows a spectral separation from the native tryptophan signal.
View Article and Find Full Text PDFTherapeutic effects of Argyrin F in pancreatic adenocarcinoma.
Cancer Lett
July 2017
Department of Internal Medicine I, Medical University Hospital, Tübingen, Germany. Electronic address:
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with limited treatment options. The proteasome inhibitor Argyrin A, a cyclic peptide derived from the myxobacterium Archangium gephyra, shows antitumoral activities. We hypothesize that his analogue Argyrin F (AF) may also prevent PDAC progression.
View Article and Find Full Text PDFA facile approach to tryptophan derivatives for the total synthesis of argyrin analogues.
Org Biomol Chem
December 2014
School of Pharmacy, Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
A facile route has been established for the synthesis of indole-substituted (S)-tryptophans from corresponding indoles, which utilizes a chiral auxiliary-facilitated Strecker amino acid synthesis strategy. The chiral auxiliary reagents evaluated were (S)-methylbenzylamine and related derivatives. To illustrate the robustness of the method, eight optically pure (S)-tryptophan analogues were synthesized, which were subsequently used for the convergent synthesis of a potent antibacterial agent, argyrin A and its analogues.
View Article and Find Full Text PDFComputational inhibition studies of the human proteasome by argyrin-based analogues with subunit specificity.
Chem Biol Drug Des
July 2014
Department of Biological Sciences, University of Cyprus, Nicosia, 1678, Cyprus.
A computational procedure was developed to study the subunit-specific interactions of the proteasome inhibitors argyrin A and F, with the aim of indentifying the determinants of subunit selectivity. Three-dimensional models of humanized proteasome active sites β1 , β2 and β5 were developed and subsequently used in molecular docking simulations with the argyrin analogues. The subunit selectivity exhibited by each analogue could be explained based on the site-specific interactions and a probability-based specificity parameter derived in this study.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!