29022-11-5Relevant articles and documents
Large molecular assembly of amphotericin B formed in ergosterol-containing membrane evidenced by solid-state NMR of intramolecular bridged derivative
Matsumori, Nobuaki,Sawada, Yuri,Murata, Michio
, p. 11977 - 11984 (2006)
Amphotericin B (AmB 1) is known to assemble and form an ion channel across biomembranes. We have recently reported that conformation-restricted derivatives of AmB 2-4 show different ergosterol preferences in ion-channel assays, which suggested that the orientation of the mycosamine strongly affects the sterol selectivity of AmB. The data allowed us to assume that compound 3 showing the highest selectivity would reflect the active conformation of AmB in the channel assembly. In this study, to gain further insight into the active conformation of AmB, we prepared a new intramolecular-bridged derivative 5, where the linker encompassed a hydrophilic glycine moiety. The derivative has almost equivalent ion-channel activity to those of AmB and 3. The antifungal activity of 5 compared with 3 improves significantly, possibly because the increasing hydrophilicity in the linker enhances the penetrability through the fungal cell wall. Conformation of 5 was well converged and very similar to that of 3, thus further supporting the notion that the conformations of these derivatives reproduce the active structure of AmB in the channel complex. Then we used the derivative to probe the mobility of AmB in the membrane by solid-state NMR. To measure dipolar couplings and chemical shift anisotropies, we incorporated [1-13C,15N]glycine into the linker. The results indicate that 5 is mostly immobilized in ergosterol-containing DMPC bilayers, implying formation of large aggregates of 5. Meanwhile some fraction of 5 remains mobile in sterol-free DMPC bilayers, suggesting promotion of Amb aggregation by ergosterol.
Synthesis and characterization of a photocleavable collagen-like peptide
Li, Chunqiang,Ornelas, Alfredo,Williams, Kaitlyn N.,Hatch, Kevin A.,Paez, Aurelio,Aguilar, Angela C.,Ellis, Cameron C.,Tasnim, Nishat,Ray, Supriyo,Dirk, Carl W.,Boland, Thomas,Joddar, Binata,Michael, Katja
, p. 1000 - 1013 (2018)
A 34-amino acid long collagen-like peptide rich in proline, hydroxyproline, and glycine, and with four photoreactive N-acyl-7-nitroindoline units incorporated into the peptide backbone was synthesized by on-resin fragment condensation. Its circular dichroism supports a stable triple helix structure. The built-in photochemical function enables the decomposition of the peptide into small peptide fragments by illumination with UV light of 350 nm in aqueous solution. Illumination of a thin film of the peptide, or a thin film of a photoreactive amino acid model compound containing a 5-bromo-7-nitroindoline moiety, with femtosecond laser light at 710 nm allows for the creation of well-resolved micropatterns. The cytocompatibility of the peptide was demonstrated using human mesenchymal stem cells and mouse embryonic fibroblasts. Our data show that the full-length peptide is cytocompatible as it can support cell growth and maintain cell viability. In contrast, the small peptide fragments created by photolysis are somewhat cytotoxic and therefore less cytocompatible. These data suggest that biomimetic collagen-like photoreactive peptides could potentially be used for growing cells in 2D micropatterns based on patterns generated by photolysis prior to cell growth.
Fungal Dioxygenase AsqJ Is Promiscuous and Bimodal: Substrate-Directed Formation of Quinolones versus Quinazolinones
Einsiedler, Manuel,Jamieson, Cooper S.,Maskeri, Mark A.,Houk, Kendall N.,Gulder, Tobias A. M.
supporting information, p. 8297 - 8302 (2021/03/01)
Previous studies showed that the FeII/α-ketoglutarate dependent dioxygenase AsqJ induces a skeletal rearrangement in viridicatin biosynthesis in Aspergillus nidulans, generating a quinolone scaffold from benzo[1,4]diazepine-2,5-dione substrates. We report that AsqJ catalyzes an additional, entirely different reaction, simply by a change in substituent in the benzodiazepinedione substrate. This new mechanism is established by substrate screening, application of functional probes, and computational analysis. AsqJ excises H2CO from the heterocyclic ring structure of suitable benzo[1,4]diazepine-2,5-dione substrates to generate quinazolinones. This novel AsqJ catalysis pathway is governed by a single substituent within the complex substrate. This unique substrate-directed reactivity of AsqJ enables the targeted biocatalytic generation of either quinolones or quinazolinones, two alkaloid frameworks of exceptional biomedical relevance.
A 4-OTBS benzyl-based protective group for carboxylic acids
Fang, Zhijun,Li, Yuyao,Xie, Hexin
supporting information, p. 1658 - 1662 (2019/05/29)
Reported herein is a novel 4-OTBS benzyl-based protective group for carboxylic acids. This protective group can be removed in the presence of TBAF or TFA with high efficiency, which makes it compatible with base-sensitive or acid-sensitive substrates. With this protective group, a near-infrared fluorogenic probe for the detection of γ-glutamyltranspeptidase activities was readily prepared.
Dihydroartemisinin and steroid conjugates, and preparation method and application thereof
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Paragraph 0098-0102, (2019/11/20)
The present invention discloses conjugates, having a general formula (I), obtained by condensation of dihydroartemisinin and steroids, or isomers or pharmaceutically acceptable salts or prodrug molecules thereof. The 10-position hydroxyl group of artemisinin and the 3-position hydroxyl group of the steroid compounds are condensed and linked by an ether bond. The invention discloses a preparation method of the compounds, and an application of the compounds in the treatment of autoimmune diseases. The dihydroartemisinin and steroid conjugates of the present invention are novel immunosuppressants, and can be used alone or in combination with other drugs to treat the human autoimmune diseases. The conjugates have the advantages of high curative effect, small toxicity and very broad applicationprospect.