- A Modular Synthetic Route Involving N-Aryl-2-nitrosoaniline Intermediates Leads to a New Series of 3-Substituted Halogenated Phenazine Antibacterial Agents
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Pathogenic bacteria demonstrate incredible abilities to evade conventional antibiotics through the development of resistance and formation of dormant, surface-attached biofilms. Therefore, agents that target and eradicate planktonic and biofilm bacteria are of significant interest. We explored a new series of halogenated phenazines (HP) through the use of N-aryl-2-nitrosoaniline synthetic intermediates that enabled functionalization of the 3-position of this scaffold. Several HPs demonstrated potent antibacterial and biofilm-killing activities (e.g., HP 29, against methicillin-resistant Staphylococcus aureus: MIC = 0.075 μM; MBEC = 2.35 μM), and transcriptional analysis revealed that HPs 3, 28, and 29 induce rapid iron starvation in MRSA biofilms. Several HPs demonstrated excellent activities against Mycobacterium tuberculosis (HP 34, MIC = 0.80 μM against CDC1551). This work established new SAR insights, and HP 29 demonstrated efficacy in dorsal wound infection models in mice. Encouraged by these findings, we believe that HPs could lead to significant advances in the treatment of challenging infections.
- Yang, Hongfen,Kundra, Shivani,Chojnacki, Michaelle,Liu, Ke,Fuse, Marisa A.,Abouelhassan, Yasmeen,Kallifidas, Dimitris,Zhang, Peilan,Huang, Guangtao,Jin, Shouguang,Ding, Yousong,Luesch, Hendrik,Rohde, Kyle H.,Dunman, Paul M.,Lemos, José A.,Huigens, Robert W.
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p. 7275 - 7295
(2021/05/29)
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- Homoallylglycine residues are superior precursors to orthogonally modified thioether containing polypeptides
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Homoallylglycine N-carboxyanhydride, Hag NCA, monomers were synthesized and used to prepare polypeptides containing Hag segments with controllable lengths of up to 245 repeats. Poly(l-homoallylglycine), GHA, was found to adopt an α-helical conf
- Perlin, Pesach,Gharakhanian, Eric G.,Deming, Timothy J.
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p. 6196 - 6199
(2018/06/18)
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- Solid phase synthesis of oligoethylene glycol-functionalized quinolinecarboxamide foldamers with enhanced solubility properties
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A series of octameric quinoline oligoamide foldamers has been synthesized consisting exclusively of monomers which display mono-, di-, tri- or tetra-ethylene glycol side-chains. These oligomers adopt stable helical conformations. New Fmoc-acid monomer precursors were first developed. The microwave assisted solid-phase synthesis (SPS) methodology for oligomer preparation is described, and it is demonstrated that small adjustments in side-chain length translate into large differences in the solubility profile of the oligomers. The impact of such modifications on foldamer preparation, handedness inversion kinetics and potential applications is also discussed.
- Tsiamantas, Christos,Dawson, Simon J.,Huc, Ivan
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p. 132 - 142
(2016/03/23)
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- Tailor-made N-heterocyclic carbenes for nanoparticle stabilization
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N-heterocyclic carbenes (NHCs) represent a leading class of ligands in organometallic chemistry, but have been rarely exploited as stabilizers for metal nanoparticles (NPs). We report the first example of NHC stabilized Pd-NPs that demonstrate long term stability. These NHC Pd-NPs were synthesized by a facile ligand exchange protocol using rationally designed long chained NHCs (LC-NHCs). Furthermore, we demonstrate that the surface modification of Pd-NPs results in significant chemoselectivity in a model reaction. The Royal Society of Chemistry 2014.
- Richter, Christian,Schaepe, Kira,Glorius, Frank,Ravoo, Bart Jan
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supporting information
p. 3204 - 3207
(2014/03/21)
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- Rapid preparation of multifunctional surfaces for orthogonal ligation by microcontact chemistry
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Microcontact chemistry has been applied to patterned glass and silicon substrates by successive reaction of unprotected and monoprotected heterobifunctional linkers with alkene-terminated self-assembled monolayers (SAMs) to produce bi-, tri-, and tetrafunctional surfaces. Photochemical microcontact printing of an azide thiol linker followed by immobilization of an acid thiol linker on an undecenyl-terminated SAM results in a well-defined, micropatterned surface with terminal azide, acid, and alkene groups. Biologically relevant molecules (biotin, carbohydrates) have been selectively attached to the surface by means of orthogonal ligation chemistry, and the resulting microarrays display selective binding to fluorescently labeled proteins. An orthogonally addressable, tetrafunctional surface (azide, acid, alkene, and amine) can be prepared by an additional printing step of a tert-butyloxycarbonyl (Boc)-protected alkyne amine linker on the azide structures by using the copper(I)-catalyzed azide-alkyne Huisgen cycloaddition and subsequent removal of the protective group. Copyright
- Wendeln, Christian,Rinnen, Stefan,Schulz, Christian,Kaufmann, Tobias,Arlinghaus, Heinrich F.,Ravoo, Bart Jan
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supporting information; experimental part
p. 5880 - 5888
(2012/07/01)
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- Ethylene glycol monolayer protected nanoparticles for eliminating nonspecific binding with biological molecules
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The usefulness of the hybrid materials of nanoparticles and biological molecules in many occasions depends on how well one can achieve a rational design based on specific binding and programmable assembly. Nonspecific binding between nanoparticles and biomolecules is one of the major barriers for achieving its utilities in a biological system. In this paper, we demonstrate a new approach to eliminate nonspecific interactions between nanoparticles and proteins by synthesizing ethylene glycol protected gold nanoparticles. We discovered that with the water content optimized in the range of 9-18% in the reaction mixture, di-, tri-, and tetra(ethylene glycol) protected gold nanoparticles Au-S-EGn (n = 2, 3, and 4) could be directly synthesized. These gold nanoparticles that are bonded with a uniform monolayer with defined length varying from 0.8 to 1.6 nm (from molecular modeling) have great stability in aqueous solutions with a high concentration of electrolyte and organic solutions. Using ion-exchange chromatography and gel electrophoresis, we demonstrated that these Au-S-EGn (n = 2, 3, or 4) nanoparticles have complete resistance to protein nonspecific interactions. These types of nanoparticles provide a fundamental starting material for designing hybrid materials composed of metallic nanoparticles and biomolecules. Copyright
- Zheng, Ming,Davidson, Fredric,Huang, Xueying
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p. 7790 - 7791
(2007/10/03)
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- Conversion of alcohols to thiols via tosylate intermediates
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High yielding syntheses of mercapto terminated mono-disperse dimer, trimer, and tetramer ethyleneoxide oligomers and of p-hydroxyphenethyl thiol via an alcohol-tosylate-thiol route are reported. Comparisons are made with the more conventional alcohol-bromide-thiol route.
- Snow, Arthur W.,Foos, Edward E.
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p. 509 - 512
(2007/10/03)
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