4023-02-3Relevant articles and documents
Design, syntheses, and transfection biology of novel non-cholesterol-based guanidinylated cationic lipids
Sen, Joyeeta,Chaudhuri, Arabinda
, p. 812 - 820 (2005)
The design of efficacious cationic transfection lipids with guanidinium headgroups is an actively pursued area of research in nonviral gene delivery. Herein, we report on the design, syntheses, and gene transfection properties of six novel non-cholesterol-based cationic amphiphiles (1-6) with a single guanidinium headgroup in transfecting CHO, COS-1, MCF-7, A549, and HepG2 cells. The in vitro gene transfer efficiencies of lipids 1-6 were evaluated using both the reporter gene and the whole cell histochemical X-gal staining assays. The efficiencies of lipids 1-3, in particular, were found to be about 2- to 4-fold higher than that of commercially available LipofectAmine in transfecting COS-1, CHO, A-549, and MCF-7 cells. However, the relative transfection efficiencies of lipids 1-3 and LipofectAmine were found to be comparable in HepG2 cells. Cholesterol was found to be a more efficacious co-lipid than dioleoyllphosphatidyl ethanolamine (DOPE). In general, lipids 1-3 containing the additional quaternized centers were observed to be more transfection efficient than lipids 4-6 with less positive headgroups. MTT-assay-based cell viability measurements in representative CHO cells revealed high (>75%) cell viabilities of lipids 1-6 across the lipid/DNA charge ratios 0.1:1 to 3:1. Electrophoretic gel patterns observed in DNase I protection experiments support the notion that enhanced degradation of DNA associated with lipoplexes of lipids 4-6 might play some role in diminishing their in vitro gene transfer efficacies. Size and global surface charge measurement by a dynamic laser light scattering instrument equipped with ζ-sizing capacity revealed the nanosizes and surface potentials of both the transfection efficient and the incompetent lipoplexes to be within the range of 200-600 nm and +3.4 to -34 mV, respectively. To summarize, given the feasibility of a wide range of structural manipulations in the headgroup regions of non-cholesterol-based cationic amphiphiles, our present findings are expected to broaden the potential of cationic amphiphiles with guanidinium headgroups for use in nonviral gene therapy.
Solvent-freeN-Boc deprotection byex situgeneration of hydrogen chloride gas
De Borggraeve, Wim M.,Gilles, Philippe,Van Mileghem, Seger,Verschueren, Rik H.
supporting information, p. 5782 - 5787 (2021/07/12)
An efficient, scalable and sustainable method for the quantitative deprotection of thetert-butyl carbamate (N-Boc) protecting group is described, using down to near-stoichiometric amounts of hydrogen chloride gas in solvent-free conditions. We demonstrate theex situgeneration of hydrogen chloride gas from sodium chloride and sulfuric acid in a two-chamber reactor, introducing a straightforward method for controlled and stoichiometric release of HCl gas. The solvent-free conditions allow deprotection of a wide variety ofN-Boc derivatives to obtain the hydrochloride salts in quantitative yields. The procedure obviates the need for any work-up or purification steps providing an uncomplicated green alternative to standard methods. Due to the solvent-free, anhydrous conditions, this method shows high tolerance towards acid sensitive functional groups and furnishes expanded functional group orthogonality.
Dimethoxyphenyl derivatives, preparation method and composition for anti-inflammatory and skin whitening comprising the same
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Paragraph 0233-0236, (2018/05/03)
The present invention relates to a dimethoxyphenyl derivatives, to a preparation method thereof, and to an anti-inflammatory and skin whitening composition comprising the same, wherein a compound represented by the chemical formula 1 according to the present invention has excellent solubility, is excellent in an effect of inhibiting the activity of NF-andkappa;B transcription factor, and thus may be useful for prevention, improvement or treatment of inflammatory diseases, and has an excellent inhibitory effect on melanin formation due to alpha-melanocyte stimulating hormone (andalpha;-MSH) inhibitory activity, thereby being useful as a cosmetic composition for preventing, improving or treating melanin pigment over-deposition disease and for whitening the skin.COPYRIGHT KIPO 2018
Conformations, conformational preferences, and conformational exchange of N′-substituted N -acylguanidines: Intermolecular interactions hold the key
Kleinmaier, Roland,Keller, Max,Igel, Patrick,Buschauer, Armin,Gschwind, Ruth M.
experimental part, p. 11223 - 11233 (2010/10/04)
Guanidine and acylguanidine groups are crucial structural features of numerous biologically active compounds. Depending on the biological target, acylguanidines may be considered as considerably less basic bioisosteres of guanidines with improved pharmacokinetics and pharmacodynamics, as recently reported for N′-monoalkylated N-acylguanidines as ligands of G-protein-coupled receptors (GPCRs). The molecular basis for enhanced ligand-receptor interactions of acylguanidines is far from being understood. So far, only a few and contradictory results about their conformational preferences have been reported. In this study, the conformations, conformational preferences, and conformational exchange of four unprotonated and seven protonated monoalkylated acylguanidines with up to six anions and with bisphosphonate tweezers are investigated by NMR. Furthermore, the effects of the acceptor properties in acylguanidine salts, of microsolvation by dimethylsulfoxide, and of varying acyl and alkyl substituents are studied. Throughout the whole study, exclusively two out of eight possible acylguanidine conformations were detected, independent of the compound, the anion, or the solvent used. For the first time, it is shown that the strength and number of intermolecular interactions with anions, solvent molecules, or biomimetic receptors decide the conformational preferences and exchange rates. One recently presented and two new crystal structures resemble the conformational preferences observed in solution. Thus, consistent conformational trends are found throughout the structurally diverse compound pool, including two potent GPCR ligands, different anions, and receptors. The presented results may contribute to a better understanding of the mechanism of action at the molecular level and to the prediction and rational design of these biologically active compounds.
PROCESS FOR STRAIGHTENING KERATIN FIBRES WITH A HEATING MEANS AND DENATURING AGENTS
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, (2010/03/02)
The invention relates to a process for straightening keratin fibres, comprising: (i) a step in which a straightening composition containing at least two denaturing agents is applied to the keratin fibres, (ii) a step in which the temperature of the keratin fibres is raised, using a heating means, to a temperature of between 110 and 250° C.
Guanidine-acylguanidine bioisosteric approach in the design of radioligands: Synthesis of a tritium-labeled NG-propionylargininamide ([3H]-UR-MK114) as a highly potent and selective neuropeptide Y Y1 receptor antagonist
Keller, Max,Pop, Nathalie,Hutzler, Christoph,Beck-Sickinger, Annette G.,Bernhardt, Günther,Buschauer, Armin
supporting information; experimental part, p. 8168 - 8172 (2009/12/07)
Synthesis and characterization of (R)-Nα-(2,2- diphenylacetyl)-N-(4-hydroxybenzyl)-Nω-([2,3- 3H]-propanoyl)-argininamide ([3H]-UR-MK114), an easily accessible tritium-labeled NPY Y1 receptor (Y1R) antagonist (KB: 0.8 nM, calcium assay, HEL cells) derived from the (R)-argininamide BIBP 3226, is reported. The radioligand binds with high affinity (KD, saturation: 1.2 nM, kinetic experiments: 1.1 nM, SK-N-MC cells) and selectivity for Y1R over Y2, Y 4, and Y5 receptors. The title compound is a useful pharmacological tool for the determination of Y1R ligand affinities, quantification of Y1R binding sites, and autoradiography.
Solvent-free synthesis of azole carboximidamides
Zahariev, Sotir,Guarnaccia, Corrado,Lamba, Doriano,?ema?ar, Ma?a,Pongor, Sándor
, p. 9423 - 9426 (2007/10/03)
A one-pot procedure is described for the preparation of azole carboximidamides 2, 3 and guanidinylation of amines with 3. The X-ray crystal structure of 3b, has been determined. A one-pot procedure is described for the preparation of 1H-pyrazole-carboximidamides 2, 1H-benzotriazole-carboximidamides 3 and guanidinylation of amines with 3. The X-ray crystal structure of N,N-dimethyl-1H-benzotriazole-1-carboximidamide 3b, has been determined.
New cellulose-supported reagent: A sustainable approach to guanidines
Porcheddu, Andrea,Giacomelli, Giampaolo,Chighine, Alessandra,Masala, Simonetta
, p. 4925 - 4927 (2007/10/03)
(Chemical Equation Presented) A new cellulose-supported reagent for the synthesis of guanidine in aqueous medium is reported starting from commercially available functionalized cellulose beads. Primary and secondary amines, anilines, and amino acids were transformed to the corresponding guanidines in high yields and under very mild conditions.
1H-Pyrazole-1-carboxamidines: New inhibitors of nitric oxide synthase
Lee, Younghee,Martasek, Pavel,Roman, Linda J,Silverman, Richard B
, p. 2771 - 2774 (2007/10/03)
1H-Pyrazole-1-carboxamidines were prepared as potential inhibitors of the three isozymes of nitric oxide synthase. All of the compounds were found to be competitive inhibitors of all three isoforms. The most selective compound prepared was 1H-pyrazole-N-(3-aminomethylanilino)-1-carboxamidine (14), which is 100-fold selective for nNOS over eNOS with a K(i) value of 2μM. (C) 2000 Elsevier Science Ltd.
