19008-71-0Relevant articles and documents
Spacer structure and hydrophobicity influences transfection activity of novel polycationic gemini amphiphiles
Puchkov, Pavel A.,Kartashova, Irina A.,Shmendel, Elena V.,Luneva, Anastasya S.,Morozova, Nina G.,Zenkova, Marina A.,Maslov, Mikhail A.
, p. 3284 - 3288 (2017)
Three novel polycationic gemini amphiphiles with different spacers were developed and evaluated in terms of their physiochemical properties and transfection efficiencies. Cationic liposomes formed by these amphiphiles and the helper lipid DOPE were able to successfully condense DNA, as shown by gel mobility shift and ethidium bromide intercalation assays. Transfection activity of the liposomes was superior to Lipofectamine 2000 and was dependent on spacer structure, hydrophobicity, and nucleic acid type (pDNA or siRNA). We demonstrated that the cationic liposomes 2X6/DOPE and 2X7/DOPE are potential non-toxic vehicles for gene delivery.
Multi-enzymatic cascade reactions with Escherichia coli-based modules for synthesizing various bioplastic monomers from fatty acid methyl esters?
Jung, Hyunsang,Kim, Byung-Gee,Kim, Ye Chan,Park, Beom Gi,Patil, Mahesh D.,Sarak, Sharad,Yoo, Hee-Wang,Yun, Hyungdon
supporting information, p. 2222 - 2231 (2022/04/03)
Multi-enzymatic cascade reaction systems were designed to generate biopolymer monomers using Escherichia coli-based cell modules, capable of carrying out one-pot reactions. Three cell-based modules, including a ω-hydroxylation module (Cell-Hm) to convert fatty acid methyl esters (FAMEs) to ω-hydroxy fatty acids (ω-HFAs), an amination module (Cell-Am) to convert terminal alcohol groups of the substrate to amine groups, and a reduction module (Cell-Rm) to convert the carboxyl groups of fatty acids to alcohol groups, were constructed. The product-oriented assembly of these cell modules involving multi-enzymatic cascade reactions generated ω-ADAs (up to 46 mM), α,ω-diols (up to 29 mM), ω-amino alcohols (up to 29 mM) and α,ω-diamines (up to 21 mM) from 100 mM corresponding FAME substrates with varying carbon chain length (C8, C10, and C12). Finally 12-ADA and 1,12-diol were purified with isolated yields of 66.5% and 52.5%, respectively. The multi-enzymatic cascade reactions reported herein present an elegant ‘greener’ alternative for the biosynthesis of various biopolymer monomers from renewable saturated fatty acids.
Concurrent Formation of N-H Imines and Carbonyl Compounds by Ruthenium-Catalyzed C-C Bond Cleavage of β-Hydroxy Azides
Lee, Jeong Min,Bae, Dae Young,Park, Jin Yong,Jo, Hwi Yul,Lee, Eunsung,Rhee, Young Ho,Park, Jaiwook
supporting information, p. 4608 - 4613 (2020/06/05)
A commercial cyclopentadienylrutenium dicarbonyl dimer ([CpRu(CO)2]2) efficiently catalyzes the formation of N-H imines and carbonyl compounds simultaneously from β-hydroxy azides via C-C bond cleavage under visible light. Density functional theory calculations for the cleavage reaction support the mechanism involving chelation of alkoxy azide species and liberation of nitrogen as the driving force. The synthetic utility of the reaction was demonstrated by a new amine synthesis promoted by chemoselective allylation of imine and synthesis of isoquinoline.
Novel BQCA- and TBPB-Derived M1 Receptor Hybrid Ligands: Orthosteric Carbachol Differentially Regulates Partial Agonism
Schramm, Simon,Agnetta, Luca,Bermudez, Marcel,Gerwe, Hubert,Irmen, Matthias,Holze, Janine,Littmann, Timo,Wolber, Gerhard,Tr?nkle, Christian,Decker, Michael
, p. 1349 - 1358 (2019/07/12)
Recently, investigations of the complex mechanisms of allostery have led to a deeper understanding of G protein-coupled receptor (GPCR) activation and signaling processes. In this context, muscarinic acetylcholine receptors (mAChRs) are highly relevant due to their exemplary role in the study of allosteric modulation. In this work, we compare and discuss two sets of putatively dualsteric ligands, which were designed to connect carbachol to different types of allosteric ligands. We chose derivatives of TBPB [1-(1′-(2-tolyl)-1,4′-bipiperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one] as M1-selective putative bitopic ligands, and derivatives of benzyl quinolone carboxylic acid (BQCA) as an M1 positive allosteric modulator, varying the distance between the allosteric and orthosteric building blocks. Luciferase protein complementation assays demonstrated that linker length must be carefully chosen to yield either agonist or antagonist behavior. These findings may help to design biased signaling and/or different extents of efficacy.
Fluorescent Benzothiazinone Analogues Efficiently and Selectively Label Dpre1 in Mycobacteria and Actinobacteria
Sommer, Raphael,Neres, Joao,Piton, Jérémie,Dhar, Neeraj,Van Der Sar, Astrid,Mukherjee, Raju,Laroche, Thierry,Dyson, Paul J.,McKinney, John D.,Bitter, Wilbert,Makarov, Vadim,Cole, Stewart T.
, p. 3184 - 3192 (2018/11/03)
Benzothiazinones (BTZ) are highly potent bactericidal inhibitors of mycobacteria and the lead compound, BTZ043, and the optimized drug candidate, PBTZ169, have potential for the treatment of tuberculosis. Here, we exploited the tractability of the BTZ scaffold by attaching a range of fluorophores to the 2-substituent of the BTZ ring via short linkers. We show by means of fluorescence imaging that the most advanced derivative, JN108, is capable of efficiently labeling its target, the essential flavoenzyme DprE1, both in cell-free extracts and after purification as well as in growing cells of different actinobacterial species. DprE1 displays a polar localization in Mycobacterium tuberculosis, M. marinum, M. smegmatis, and Nocardia farcinica but not in Corynebacterium glutamicum. Finally, mutation of the cysteine residue in DprE1 in these species, to which BTZ covalently binds, abolishes completely the interaction with JN108, thereby highlighting the specificity of this fluorescent probe.
Parallel anti-sense two-step cascade for alcohol amination leading to ω-amino fatty acids and α,ω-diamines
Sung, Sihyong,Jeon, Hyunwoo,Sarak, Sharad,Ahsan, Md Murshidul,Patil, Mahesh D.,Kroutil, Wolfgang,Kim, Byung-Gee,Yun, Hyungdon
supporting information, p. 4591 - 4595 (2018/10/23)
Running two two-step cascades in parallel anti-sense to transform an alcohol to an amine allowed the conversion of ω-hydroxy fatty acids (ω-HFAs) and α,ω-diols to the corresponding ω-amino fatty acids (ω-AmFAs) and α,ω-diamines, respectively. The network required only two enzymes namely an aldehyde reductase (AHR) and a transaminase (TA). Benzylamine served on the one hand as amine donor and on the other hand after deamination to benzaldehyde also as oxidant. All ω-HFAs tested were efficiently transformed to their corresponding ω-AmFAs using purified enzymes as well as a whole-cell system, separately expressing both the enzymes, with conversions ranging from 80-95%. Additionally, a single-cell co-expressing all enzymes successfully produced the ω-AmFAs as well as the α,ω-diamines with >90% yield. This system was extended by employing a lactonase, enabling the transformation of ?-caprolactone to its corresponding ω-AmFA with >80% conversion.
Hydroxypyridinone and 5-Aminolaevulinic Acid Conjugates for Photodynamic Therapy
Battah, Sinan,Hider, Robert C.,MacRobert, Alexander J.,Dobbin, Paul S.,Zhou, Tao
, p. 3498 - 3510 (2017/05/05)
Photodynamic therapy (PDT) is a promising treatment strategy for malignant and nonmalignant lesions. 5-Aminolaevulinic acid (ALA) is used as a precursor of the photosensitizer, protoporphyrin IX (PpIX), in dermatology and urology. However, the effectiveness of ALA-PDT is limited by the relatively poor bioavailability of ALA and rapid conversion of PpIX to haem. The main goal of this study was to prepare and investigate a library of single conjugates designed to coadminister the bioactive agents ALA and hydroxypyridinone (HPO) iron chelators. A significant increase in intracellular PpIX levels was observed in all cell lines tested when compared to the administration of ALA alone. The higher PpIX levels observed using the conjugates correlated well with the observed phototoxicity following exposure of cells to light. Passive diffusion appears to be the main mechanism for the majority of ALA-HPOs investigated. This study demonstrates that ALA-HPOs significantly enhance phototherapeutic metabolite formation and phototoxicity.
Polyvalent Azasugar derivatives and its synthetic method
-
, (2017/01/31)
The invention provides derivatives of multivalent azasugar of 3,4,5-trihydroxyl-1-octylpiperidine-2-ketone having a general formula (I), and a synthetic method of the derivatives. According to the derivatives and the preparation method thereof provided by the invention, multivalent azasugar is formed by connecting (3S,4R,5S)-3,4,5-trihydroxyl-1-(8-aminooctyl)piperidine-2-ketone as a monomer with a polyatomic acid or polyacyl chloride, or connecting (3S,4R,5S)-3,4,5-trihydroxyl-1-(8-azidooctyl)piperidine-2-ketone as a monomer with a derivative of a polyatomic acid, polyhydric alcohol or polyacyl chloride The multivalent azasugar synthesized by the method provided by the invention has the potential of serving as a pharmacological molecular chaperone in CMT (Pharmacological Chaperone Molecular therapy) for treating Gaucher disease, and thereby having a high application value.
ISOTHIOCYANATE COMPOUNDS, PHARMACEUTICAL COMPOSITIONS, AND USES THEREOF
-
, (2015/10/05)
Provided herein are compositions of matter and pharmaceutical compositions thereof, for use in inhibiting the growth of various microbial pathogens, including bacteria, fungi, protozoa, and viral pathogens. Also provided herein are methods of treating microbial diseases/infections and cancer with the compositions. The compositions are additionally useful in wood preservation and food preservation by inhibition of microbial growth.
Redox self-sufficient biocatalyst network for the amination of primary alcohols
Sattler, Johann H.,Fuchs, Michael,Tauber, Katharina,Mutti, Francesco G.,Faber, Kurt,Pfeffer, Jan,Haas, Thomas,Kroutil, Wolfgang
supporting information, p. 9156 - 9159 (2012/10/30)
Driving the machinery: A biocatalytic redox-neutral cascade for the preparation of terminal primary amines from primary alcohols at the expense of ammonia has been established in a one-pot one-step method (see picture). Applying this artificial biocatalyst network, long-chain 1,ω-alkanediols were converted into diamines, which are building blocks for polymers, in up to 99 % conversion. Copyright
