179087-83-3Relevant academic research and scientific papers
Flexizyme-Enabled Benchtop Biosynthesis of Thiopeptides
Fleming, Steven R.,Bartges, Tessa E.,Vinogradov, Alexander A.,Kirkpatrick, Christine L.,Goto, Yuki,Suga, Hiroaki,Hicks, Leslie M.,Bowers, Albert A.
, p. 758 - 762 (2019)
Thiopeptides are natural antibiotics that are fashioned from short peptides by multiple layers of post-translational modification. Their biosynthesis, in particular the pyridine synthases that form the macrocyclic antibiotic core, has attracted intensive research but is complicated by the challenges of reconstituting multiple-pathway enzymes. By combining select RiPP enzymes with cell free expression and flexizyme-based codon reprogramming, we have developed a benchtop biosynthesis of thiopeptide scaffolds. This strategy side-steps several challenges related to the investigation of thiopeptide enzymes and allows access to analytical quantities of new thiopeptide analogs. We further demonstrate that this strategy can be used to validate the activity of new pyridine synthases without the need to reconstitute the cognate prior pathway enzymes.
Gatorbulin-1, a distinct cyclodepsipeptide chemotype, targets a seventh tubulin pharmacological site
Matthew, Susan,Chen, Qi-Yin,Ratnayake, Ranjala,Fermaintt, Charles S.,Lucena-Agell, Daniel,Bonato, Francesca,Prota, Andrea E.,Lim, Seok Ting,Wang, Xiaomeng,Díaz, J. Fernando,Risinger, April L.,Paul, Valerie J.,Oliva, Maria ángela,Luesch, Hendrik
, (2021/03/03)
Tubulin-targeted chemotherapy has proven to be a successful and wide spectrum strategy against solid and liquid malignancies. Therefore, new ways to modulate this essential protein could lead to new antitumoral pharmacological approaches. Currently known tubulin agents bind to six distinct sites at α/β-tubulin either promoting microtubule stabilization or depolymerization. We have discovered a seventh binding site at the tubulin intradimer interface where a novel microtubule-destabilizing cyclodepsipeptide, termed gatorbulin-1 (GB1), binds. GB1 has a unique chemotype produced by a marine cyanobacterium. We have elucidated this dual, chemical and mechanistic, novelty through multidimensional characterization, starting with bioactivity-guided natural product isolation and multinuclei NMR-based structure determination, revealing the modified pentapeptide with a functionally critical hydroxamate group; and validation by total synthesis. We have investigated the pharmacology using isogenic cancer cell screening, cellular profiling, and complementary phenotypic assays, and unveiled the underlying molecular mechanism by in vitro biochemical studies and high-resolution structural determination of the α/β-tubulin?GB1 complex.
ANTIBACTERIAL COMPOUNDS
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Page/Page column 28, (2018/10/19)
Novel compounds having antimicrobial activitiy, in particular against Pseudomonas aeruginosa, Burkholderia cepaciaand/or Clostridium difficile, and a pharmaceutical composition containing the novel compound.
Straightforward method for the synthesis of selenocysteine and selenocystine derivatives from L-serine methyl ester
Braga, Antonio L.,Wessjohann, Ludger A.,Taube, Paulo S.,Galetto, Fabio Z.,De Andrade, Fabiano M.
scheme or table, p. 3131 - 3137 (2010/11/02)
A set of selenoamino acids has been efficiently synthesized under smooth conditions by a simple, flexible and modular strategy. In this method, O-mesylated l-serine methyl ester is generated in situ and directly substituted with various selenolate anions
Internally stabilized selenocysteine derivatives: Syntheses, 77Se NMR and biomimetic studies
Phadnis, Prasad P.,Mugesh
, p. 2476 - 2481 (2007/10/03)
Selenocystine ([Sec]2) and aryl-substituted selenocysteine (Sec) derivatives are synthesized, starting from commercially available amino acid L-serine. These compounds are characterized by a number of analytical techniques such as NMR (1H, 13C and 77Se) and TOF mass spectroscopy. This study reveals that the introduction of amino/imino substituents capable of interacting with selenium may stabilize the Sec derivatives. This study further suggests that the oxidation-elimination reactions in Sec derivatives could be used for the generation of biologically active selenols having internally stabilizing substituents. The Royal Society of Chemistry 2005.
Synthetic studies on thiostrepton family of peptide antibiotics: Synthesis of the cyclic core portion containing the dehydropiperidine, dihydroquinoline, L-valine, and masked dehydroalanine segments
Mori, Tomonori,Tohmiya, Hiraku,Satouchi, Yukiko,Higashibayashi, Shuhei,Hashimoto, Kimiko,Nakata, Masaya
, p. 6423 - 6427 (2007/10/03)
The cyclic core portion containing the dehydropiperidine, dihydroquinoline, L-valine, and masked dehydroalanine (i.e., β-phenylselenoalanine) segments of the thiostrepton family of peptide antibiotics was synthesized via the consecutive coupling of these four segments followed by cyclization at the amide bond between the dehydropiperidine and masked dehydroalanine segments.
Total synthesis of the cyclic heptapeptide Argyrin B: A new potent inhibitor of T-cell independent antibody formation
Ley, Steven V.,Prieur, Alain,Heusser, Christoph
, p. 711 - 714 (2007/10/03)
(equation presented) Argyrin B (1) The total synthesis of Argyrin B (1) is presented using a synthetic plan that is convergent and flexible and conserves the stereogenic centers. The unusual amino acid 4-methoxy tryptophan (6) was obtained via an enzymati
Total synthesis of the cyclic peptide Argyrin B
Ley, Steven V.,Priour, Alain
, p. 3995 - 4004 (2007/10/03)
The details of the total synthesis of Argyrin B, a natural product with immunosuppressive properties, are reported below. The two most unusual amino acid residues of this cyclic peptide are 4-methoxytryptophan and dehydroalanine, which were obtained by mo
Facile chemoselective synthesis of dehydroalanine-containing peptides.
Okeley,Zhu,van Der Donk
, p. 3603 - 3606 (2007/10/03)
Useful methodology is described for the synthesis of dehydroalanine residues (II) within peptides. The unnatural amino acid (Se)-phenylselenocysteine (I) can be incorporated into growing peptide chains via standard peptide synthesis procedures. Subsequent
Synthesis of optically pure β-phenylselenoalanine through serine-β-lactone: A useful precursor of dehydroalanine
Sakai, Mitsuru,Hashimoto, Kimiko,Shirahama, Haruhisa
, p. 319 - 324 (2007/10/03)
Optically pure L- and D-β-phenylselenoalanines (PhSeAla), useful precursors of dehydroalanine, were synthesized from L- and D-serine-β-lactone. Elimination reactions of the phenylseleno group to form the dehydroalanine were examined.
