- L-serine and glycine based ceramide analogues as transdermal permeation enhancers: Polar head size and hydrogen bonding
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Novel transdermal permeation enhancers related to stratum corneum ceramides were investigated. The synthesis of a series of simple compounds based on two selected amino acids, L-serine and glycine, and their enhancement activities are reported. Glycine derivative 3 enhanced the permeation of theophylline through human skin in vitro 12.5±0.5 times. The relationships between properties of the polar head of the compounds and their activity are discussed.
- Vavrova, Katerina,Hrabalek, Alexandr,Dolezal, Pavel,Holas, Tomas,Zbytovska, Jarmila
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- The Study of Stability of Proline-Containing Derivatives of Dopamine and Serotonin in the Biological Media in Vitro Experiments
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Abstract—: The peptides Boc-Gly-Pro-DP, Z-Gly-Pro-DP, LA-Gly-Pro-DP, Boc-Gly-Pro-Srt, Z-Gly-Pro-Srt have been synthesized for the first time. The study of their stability in the presence of leucine aminopeptidase, carboxypeptidase Y, carboxypeptidase B, and proline endopeptidase (PEP) has shown that the synthesized peptides are stable in the presence of aminopeptidases and carboxypeptidases. In the presence of PEP, dopamine (DP) and serotonin (Srt) have been cleaved from these substances. Thus, the originally synthesized proline derivatives of Srt and DP may be considered as the resources, from which Srt and DP can be gradually released. This creates the possibility of a prolonged action of these biologically active compounds on cells and, consequently, on the whole body.
- Andreeva, L. A.,Myasoedov, N. F.,Nagaev, I. Yu.,Shevchenko, K. V.,Shevchenko, V. P.
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- Glucosamine anchored cancer targeted nano-vesicular drug delivery system of doxorubicin
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Background: Efficacy of an anticancer drug is challenged by severe adverse effects persuaded by the drug itself; hence designing a tumour targeted delivery system is chosen as an objective of this research work.Purpose: We propose, glucose transporter targeting ligand, i.e. synthesised N-lauryl glucosamine (NLG) anchored doxorubicin (DOX) in niosomal formulation.Methods: Synthesised NLG was incorporated into niosomal formulation of DOX using Span 60 as surfactant, cholesterol as membrane stabilizer and dicetyl phosphate (DCP) as stabilizer.Results: The formulation was stable with particle size of 110 ± 5 nm, zeta potential -30 ± 5 mV and entrapment efficiency approximately 95%. DSC and XRD pattern of freeze-dried formulation demonstrated encapsulation of DOX in niosomal formulation. Cytotoxicity of targeted niosomal formulation (IC50 = 0.830 ppm) was higher than non-targeted niosomal formulation (IC50 = 1.369 ppm) against B6F10 melanoma cell lines. In vitro cellular internalization revealed that targeted niosomal formulation was internalised more efficiently with higher cellular retention by cancer cells compared to the non-targeted niosomal formulation and free DOX. In vitro receptor binding and docking study of targeted niosomal formulation had shown the comparative association potential with glucose receptor.Conclusion: NLG anchored niosomal formulation of DOX with enhanced cytotoxicity, internalization and receptor binding potential has implication in targeted cancer therapy.
- Pawar, Smita,Vavia, Pradeep
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- Dendrimeric pyridoxamine enzyme mimics
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PAMAM dendrimers from generations 1-6 were synthesized with pyridoxamine in their core. They transaminated pyruvic and phenylpyruvic acids in water to alanine and phenylalanine, respectively, with Michaelis-Menten kinetics and high effectiveness compared with simple pyridoxamine. The largest dendrimerssimilar in size to some globular proteinswere comparable in effectiveness to a previous polyethylenimine (PEI)-pyridoxamine catalyst, and to a protein-pyridoxamine catalyst, but not as effective as a previous PEI-pyridoxamine carrying lauryl hydrophobic groups. The new catalysts showed both general acid/base catalysis by their amino groups and hydrophobic binding of the phenylpyruvate substrate. Copyright
- Liu, Lei,Breslow, Ronald
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- Encapsulation of paclitaxel into lauric acid-O-carboxymethyl chitosan-transferrin micelles for hydrophobic drug delivery and site-specific targeted delivery
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Transferrin/PEG/O-carboxymethyl chitosan/fatty acid/paclitaxel (TPOCFP) micelles were tested for suitability as a drug carrier characterized by low cytotoxicity, sustained release, high cellular uptake, and site-specific targeted delivery of hydrophobic drugs. Characterization, drug content, encapsulation efficiency, and in vitro drug release were investigated. When the feeding amount of paclitaxel (PTX) was increased, the drug content increased, but loading efficiency decreased. TPOCFP micelles had a spherical shape, with a particle size of approximately 140-649 nm. In vitro cell cytotoxicity and hemolysis assays were conducted to confirm the safety of the micelles. Anticancer activity and confocal laser scanning microscopy (CLSM) were used to confirm the targeting efficiency of target ligand-modified TPOCFP micelles. Anticancer activity and CLSM results clearly demonstrated that transferrin-modified TPOCFP micelles were quickly taken up by the cell. The endocytic pathway of TPOCFP micelles was analyzed by flow cytometry, revealing transfection via receptor-mediated endocytosis. These results suggest that PTX-encapsulated TPOCFP micelles may be used as an effective cancer-targeting drug delivery system for chemotherapy.
- Nam, Joung-Pyo,Park, Seong-Cheol,Kim, Tae-Hun,Jang, Jae-Yeang,Choi, Changyong,Jang, Mi-Kyeong,Nah, Jae-Woon
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- Convenient synthesis of N-hydroxysuccinimide esters from carboxylic acids using triphosgene
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A simple and convenient method for the synthesis of N-hydroxysuccinimide ester is developed using triphosgene as an acid activator. Several aromatic and aliphatic N-hydroxysuccinimide esters are prepared from their corresponding carboxylic acids at room temperature in good yields in a rapid process using triphosgene. Some of the major advantages are mild conditions, good yields, and easy operation.
- Kim, Misoo,Han, Ki-Jong
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- Development of small-molecule inhibitors of fatty acyl-AMP and fatty acyl-CoA ligases in Mycobacterium tuberculosis
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Lipid metabolism in Mycobacterium tuberculosis (Mtb) relies on 34 fatty acid adenylating enzymes (FadDs) that can be grouped into two classes: fatty acyl-CoA ligases (FACLs) involved in lipid and cholesterol catabolism and long chain fatty acyl-AMP ligases (FAALs) involved in biosynthesis of the numerous essential and virulence-conferring lipids found in Mtb. The precise biochemical roles of many FACLs remain poorly characterized while the functionally non-redundant FAALs are much better understood. Here we describe the systematic investigation of 5′-O-[N-(alkanoyl)sulfamoyl]adenosine (alkanoyl adenosine monosulfamate, alkanoyl-AMS) analogs as potential multitarget FadD inhibitors for their antitubercular activity and biochemical selectivity towards representative FAAL and FACL enzymes. We identified several potent compounds including 12-azidododecanoyl-AMS 28, 11-phenoxyundecanoyl-AMS 32, and nonyloxyacetyl-AMS 36 with minimum inhibitory concentrations (MICs) against M. tuberculosis ranging from 0.098 to 3.13 μM. Compound 32 was notable for its impressive biochemical selectivity against FAAL28 (apparent Ki = 0.7 μM) versus FACL19 (Ki > 100 μM), and uniform activity against a panel of multidrug and extensively drug-resistant TB strains with MICs ranging from 3.13 to 12.5 μM in minimal (GAST) and rich (7H9) media. The SAR analysis provided valuable insights for further optimization of 32 and also identified limitations to overcome.
- Aldrich, Courtney C.,Baran, Marzena,Boshoff, Helena I. M.,Fu, Peng,Grimes, Kimberly D.,Sibbald, Paul A.,Wilson, Daniel J.
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- COMPOSITIONS AND METHODS FOR THE TREATMENT OF INFLAMMATORY SKIN DISEASES AND CANCER
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The invention relates to the compounds or its pharmaceutical acceptable polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I, formula II formula III, formula IV, formula V, formula VI, formula VII, and formula VIII and the methods for the treatment of inflammatory skin diseases and cancer may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, lozenge, spray, intravenous, oral solution, nasal spray, oral solution, suspension, oral spray, buccal mucosal layer tablet, parenteral administration, syrup, or injection. Such compositions may be used to treatment of facial hirsutism, GI Polyps, rosacea, acne, melanoma, psoriasis, dermatitis and cancer including gliomas, gastrointestinal polyps, anaplastic astrocytoma and metastatic cancers.
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Paragraph 00116
(2020/01/11)
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- A reagent for analysis of blood and preparation method therof
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The present invention relates to a compound for hemanalysis, capable of lysing blood cells except leukocytes without globulolysis of leukocytes. The present invention further relates to a production method thereof. According to various embodiments of the present invention, the compound can lyse every blood cell except the leukocyte without globulolysis of leukocyte, thereby being selectively applicable to various fields. In addition, a kit or a composition for globulolysis using the compound and a kit or a composition for hemanalysis exhibit excellent efficiency compared to conventional counterparts. To this end, the compound is represented by chemical formula 14 or 15.COPYRIGHT KIPO 2018
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Paragraph 0138; 0139; 0141; 0142
(2018/08/07)
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- Synthesis and Characterization of Fatty Acid Grafted Chitosan Polymer and Their Nanomicelles for Nonviral Gene Delivery Applications
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The aim of this study was to synthesize and characterize fatty acid-grafted-chitosan (fatty acid-g-CS) polymer and their nanomicelles for use as carriers for gene delivery. CS was hydrophobically modified using saturated fatty acids of increasing fatty acyl chain length. Carbodiimide along with N-hydroxysuccinimide was used for coupling carboxyl group of fatty acids with amine groups of CS. Proton nuclear magnetic resonance and Fourier transform infrared spectroscopy were used to quantify fatty acyl substitution onto CS backbone. The molecular weight distribution of the synthesized polymers was determined using size exclusion high performance liquid chromatography and was found to be in range of the parent CS polymer (~50 kDa). The critical micelle concentration (cmc) of the polymers was determined using pyrene as a fluorescent probe. The cmc was found to decrease with an increase in fatty acyl chain length. The amphiphilic fatty acid-g-CS polymers self-assembled in an aqueous environment to form nanomicelles of ~200 nm particle size and slightly positive net charge due to the cationic nature of free primary amino groups on CS molecule. These polymeric nanomicelles exhibited excellent hemo- and cytocompatibility, as evaluated by in vitro hemolysis and MTT cell viability assay, respectively, and showed superior transfection efficiency compared to unmodified chitosan and naked DNA. The surface of these nanomicelles can be further modified with ligands allowing for selective targeting, enhanced cell binding, and internalization. These nanomicelles can thus be exploited as potential nonviral gene delivery vectors for safe and efficient gene therapy.
- Sharma, Divya,Singh, Jagdish
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p. 2772 - 2783
(2017/11/20)
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- Biosynthetic Studies of Telomycin Reveal New Lipopeptides with Enhanced Activity
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Telomycin (TEM) is a cyclic depsipeptide antibiotic active against Gram-positive bacteria. In this study, five new natural telomycin analogues produced by Streptomyces canus ATCC 12646 were identified. To understand the biosynthetic machinery of telomycin and to generate more analogues by pathway engineering, the TEM biosynthesis gene cluster has been characterized from S. canus ATCC 12646: it spans approximately 80.5 kb and consists of 34 genes encoding fatty acid ligase, nonribosomal peptide synthetases (NRPSs), regulators, transporters, and tailoring enzymes. The gene cluster was heterologously expressed in Streptomyces albus J1074 setting the stage for convenient biosynthetic engineering, mutasynthesis, and production optimization. Moreover, in-frame deletions of one hydroxylase and two P450 monooxygenase genes resulted in the production of novel telomycin derivatives, revealing these genes to be responsible for the specific modification by hydroxylation of three amino acids found in the TEM backbone. Surprisingly, natural lipopeptide telomycin precursors were identified when characterizing an unusual precursor deacylation mechanism during telomycin maturation. By in vivo gene inactivation and in vitro biochemical characterization of the recombinant enzyme Tem25, the maturation process was shown to involve the cleavage of previously unknown telomycin precursor-lipopeptides, to yield 6-methylheptanoic acid and telomycins. These lipopeptides were isolated from an inactivation mutant of tem25 encoding a (de)acylase, structurally elucidated, and then shown to be deacylated by recombinant Tem25. The TEM precursor and several semisynthetic lipopeptide TEM derivatives showed rapid bactericidal killing and were active against several multidrug-resistant (MDR) Gram-positive pathogens, opening the path to future chemical optimization of telomycin for pharmaceutical application. (Chemical Equation Presented).
- Fu, Chengzhang,Keller, Lena,Bauer, Armin,Br?nstrup, Mark,Froidbise, Alexandre,Hammann, Peter,Herrmann, Jennifer,Mondesert, Guillaume,Kurz, Michael,Schiell, Matthias,Schummer, Dietmar,Toti, Luigi,Wink, Joachim,Müller, Rolf
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supporting information
p. 7692 - 7705
(2015/07/01)
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- A systematic understanding of gelation self-assembly: solvophobically assisted supramolecular gelation via conformational reorientation across amide functionality on a hydrophobically modulated dipeptide based ambidextrous gelator, N-n-acyl-(l)Val-X(OBn), (X = 1,ω-amino acid)
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A systematic investigation on gelation self-assembly has been performed on a hydrophobically modulated dipeptide based ambidextrous gelator, N-n-acyl-(l)Val-X(OBn), (X = 1,ω-amino acid). To elucidate the effect of hydrophobic tuning on gelator architecture towards its gelation self-assembly, three sets of gelators with a common formula: CmH2m+1C(=O)NH(l)Val(C=O)NH-(CH2)n-(C=O)OBn, were synthesized, Set-I includes gelators with n = 2, m = 9, 11, 13, 15, 17, for Set-II it is n = 2, 3, 5, m = 13 and Set-III comprises of two isomeric gelators (n = 2, m = 15; n = 10, m = 7). Gelation has been critically analyzed in various apolar (aromatic and aliphatic) and polar (protic and aprotic) solvents using FESEM, CD, IR, WAXRD and rheological studies. Obtained results reveal that π-π type interaction dictates the primary molecular alignment and positioning of amide functionality across the aliphatic chain which influences the peptidic orientation in parallel (when m > n) or antiparallel (when m gel and yield stress of gel systems increases with m, but for a given m, the trend goes apparently inverse with the increasing n. Circular dichroism (CD) studies suggest an intriguing evidence of non-planarity of amide plane during self-assembly, highlighting the involvement of conformational change taking place during molecular organization towards its gelation. Despite complex nature of solvent-gelator interaction, the effect of H-bonding component of solubility parameters was found to have a significant role on self-assembly. Overall, supramolecular forces acting at specific functionalities encrypted in gelator backbone must overcome the solvation energy with synergic assistance of solvophobic effect towards stabilization of gel-network with optimum gelator backbone conformation for achieving required enthalpic contribution for self-assembly.
- Haldar, Saubhik,Karmakar, Koninika
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p. 66339 - 66354
(2015/08/18)
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- SURFACE FUNCTIONALIZED, HOST-GUEST POLYMER NANO-ASSEMBLIES AND METHODS THEREOF
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The invention generally relates to polymer-based nano-structures. More particularly, the invention relates to novel, surface-functionalized, guest-host polymer nano-assemblies and nano-delivery vehicles useful in diverse fields including drug delivery, diagnostics and specialty materials. The nano-assemblies and nano-delivery vehicles of the invention are afforded via simplify and reliable approaches.
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Paragraph 00118; 00121
(2015/09/28)
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- Peptide conjugates for directing the morphology and assembly of 1D nanoparticle superstructures
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Designed peptide conjugates molecules are used to direct the synthesis and assembly of gold nanoparticles into complex 1D nanoparticle superstructures with various morphologies. Four peptide conjugates, each based on the gold-binding peptide (AYSSGAPPMPPF
- Zhang, Chen,Song, Chengyi,Fry, H. Christopher,Rosi, Nathaniel L.
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p. 941 - 945
(2014/02/14)
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- Synthesis and physicochemical properties of new tripodal amphiphiles bearing fatty acids as a hydrophobic group
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Saturated fatty acids (FA) were grafted using tyrosine as a spacer group to the cyclotriphosphazene ring along with equimolar hydrophilic methoxy poly(ethylene glycol) (MPEG) in cis-nongeminal way. Seven new cyclotriphosphazene amphiphiles were prepared from combinations of hydrophilic MPEGs with different molecular weights of 350, 550, 750 and 1000 and four different fatty acids of different hydrophobicity including lauric, myristic, palmitic and stearic acids. These steric amphiphiles bearing fatty acids as a hydrophobic group were found to form more stable micelles with very low critical micelle concentrations (CMC) (2.95-7.80 mg/L) compared with oligopeptide analogues, and their highly hydrophobic core environment is unique and potentially useful for various biomedical applications.
- Avaji, Prakash G.,Jadhav, Vithal B.,Cui, Jin Xin,Jun, Yong Joo,Lee, Hwa Jeong,Sohn, Youn Soo
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supporting information
p. 1763 - 1767
(2013/04/10)
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- Synthesis of macrocyclic ketones exploiting palladium-catalyzed activation of carboxylic acids as an enabling step
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The novel synthesis of macrocyclic arylketones via palladium-catalyzed cross-coupling of arylboronic acids and carboxylic acids, activated by the treatment with di(N-succinimidyl) carbonate, is disclosed. This allows the high yielding synthesis of various
- Kapdi, Anant R.,Fairlamb, Ian J. S.
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supporting information
p. 961 - 964
(2013/06/27)
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- Exploring the effect of sialic acid orientation on ligand-receptor interactions
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Here, we present the synthesis of two sialo-micelles to validate the significance of sialic acid orientation during specific carbohydrate-protein and carbohydrate-carbohydrate interactions. Our data clearly suggest that orientation of carboxylic acid and
- Yadav, Rohan,Kikkeri, Raghavendra
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supporting information; experimental part
p. 7265 - 7267
(2012/08/28)
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- New parasite inhibitors encompassing novel conformationally-locked 5′-acyl sulfamoyl adenosines
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We describe the design, synthesis and biological evaluation of conformationally-locked 5′-acyl sulfamoyl adenosine derivatives as new parasitic inhibitors against Trypanosoma and Leishmania. The conformationally-locked (3′-endo, North-type) nucleosides have been synthesized by covalently attaching a 4′-CH2-O-2′ bridge (Fig. 2) across C2′-C4′ of adenosine in order to reduce the conformational flexibility of the pentose ring. This is designed to decrease the entropic penalty for complex formation with the target protein, which may improve free-energy of stabilization of the complex leading to improved potency. Conformationally-locked 5′-acyl sulfamoyl adenosine derivatives (16-22) were tested against parasitic protozoans for the first time in this work, and showed potent inhibition of Trypanosoma cruzi, Trypanosoma brucei, Trypanosoma rhodesiense and Leishmania infantum with IC50 = 0.25-0.51 μM. In particular, the potent 5′-pentanyl acyl sulfamoyl adenosine derivative 17 (IC50 = 0.25 μM) against intracellular L. infantum amastigotes and Trypanosoma subspecies is interesting in view of its almost insignificant cytotoxicity in murine macrophage host cells (CC50 >4 μM) and in diploid human fibroblasts MRC-5 cell lines (CC50 4 μM). This work also suggests that variable alkyl chain length of the acyl group on the acylsulfamoyl side chain at 5′ can modulate the toxicity of 5′-O-sulfamoylnucleoside analogues. This conformationally-locked sulfamoyl adenosine scaffold presents some interesting possibilities for further drug design and lead optimization.
- Dixit, Shailesh S.,Upadhayaya, Ram Shankar,Chattopadhyaya, Jyoti
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experimental part
p. 6121 - 6129
(2012/09/05)
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- Functionalization of poly(amidoamine) dendrimers with hydrophobic chains for improved gene delivery in mesenchymal stem cells
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A new family of gene delivery vectors is synthesized consisting of a medium-size generation PAMAM dendrimer (generation 5, with amine termini) core randomly linked at the periphery to hydrophobic chains that vary in length (12 to 16 carbon alkyl chains) and number (from 4.2 to 9.7 in average). The idea subjacent to the present work is to join the advantages of the cationic nature of the dendrimer with the capacity of lipids to interact with biological membranes. Unlike other amphiphilic systems designed for the same purpose, where the hydrophobic and hydrophilic moieties coexist in opposite sides, the present vectors have a hydrophilic interior and a hydrophobic corona. The vectors are characterized in respect to their ability to neutralize, bind and compact plasmid DNA (pDNA). The complexes formed between the vectors and pDNA are analyzed concerning their size, ζ-potential, resistance to serum nucleases, capacity of being internalized by cells and transfection efficiency. These new vectors show a remarkable capacity for mediating the internalization of pDNA with minimum cytotoxicity, being this effect positively correlated with the -CH2- content present in the hydrophobic corona. Gene expression in MSCs, a cell type with relevancy in the regenerative medicine clinical context, is also enhanced using the new vectors but, in this case, the higher efficiency is shown by the vectors containing the smallest hydrophobic chains.
- Santos, José L.,Oliveira, Hugo,Pandita, Deepti,Rodrigues, Jo?o,Pêgo, Ana P.,Granja, Pedro L.,Tomás, Helena
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scheme or table
p. 55 - 64
(2011/10/31)
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- Synthesis of lipoamino acids and their activity against cerebral ischemic injury
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A series of lipoamino acids were synthesized and their neuroprotective effect against brain ischemia induced by oxygen-glucose deprivation (OGD) on rat cerebral slices was evaluated. Among these compounds, N-stearoyl-L-tyrosine (4), N-stearoyl-L-serine (5) and N-stearoyl-L-threonine (6) exhibited good neuroprotective activity. We found that the neuroprotective activity of lipoamino acids depended on the acyl group, the presence of a free carboxylic function and a free hydroxyl group at the branched chain of the amino acids. The results also showed that 5 was the most active compound, protecting rat brain slices against OGD as well as hydrogen peroxide (H2O2) insult at the range of 1-10 M.
- Yao, Li-Yun,Lin, Qi,Niu, Yin-Yao,Deng, Ke-Min,Zhang, Jian-Hua,Lu, Yang
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experimental part
p. 4051 - 4064
(2009/12/26)
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- The effect of unsaturation on the formation of self-assembled gels from fatty acid L-serine amides and their cytotoxicity towards caco-2 cancer cells
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A series of saturated and unsaturated fatty acid l-serines 3 were synthesized and their ability to form self-assembled gels was investigated. The saturated (lauroyl 3a and steraoyl 3b) and monounsaturated (oleoyl 3c) fatty acid l-serines form gels in both water and organic solvent, whereas the diunsaturated linoleyl-l-serine 3d does not form gels in these solvents, indicating that unsaturation adversely affects the gelation process. Cytotoxicity studies on these compounds with Caco-2 cancer cells in vitro show that these gels are only moderately cytotoxic at concentrations up to 0.5 mM, making them a promising candidate for applications such as drug delivery. CSIRO 2009.
- Lim, Li Yun Grace,Su, Yingying,Braet, Filip,Thordarson, Pall
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scheme or table
p. 653 - 656
(2010/01/16)
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- 2′-Lipid-modified oligonucleotides via a 'Staudinger-Vilarrasa' reaction
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We report a new access to 2′-amido-2′-deoxyuridine via a Staudinger-Vilarrasa coupling reaction for the preparation of lipid-modified oligonucleotides. One or two lipidic moieties were inserted within the oligonucleotidic sequence (LONs) leading to a repertoire of original antagomir-like molecules targeting micro RNA (miRNA or miR). Melting temperature (Tm) experiments revealed that the stability of the duplexes depends on the lipid position and the number of lipid moieties inserted within the oligonucleotide sequence. Single lipid conjugations of positions 11 and 19 of LONs targeting miR-122 do not destabilize the duplexes.
- Chapuis, Hubert,Bui, Laurent,Bestel, Isabelle,Barthélémy, Philippe
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supporting information; scheme or table
p. 6838 - 6840
(2009/04/07)
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- A new peptide-based method for the design and synthesis of nanoparticle superstructures: Construction of highly ordered gold nanoparticle double helices
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Left-handed gold nanoparticle double helices were prepared using a new method that allows simultaneous synthesis and assembly of discrete nanoparticles. This method involves coupling the processes of peptide self-assembly of and peptide-based biomineraliz
- Chen, Chun-Long,Zhang, Peijun,Rosi, Nathaniel L.
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supporting information; body text
p. 13555 - 13557
(2009/02/06)
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- Synthetic libraries of tyrosine-derived bacterial metabolites
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The preparation of a collection of 131 small molecules, reminiscent of families of long chain N-acyl tyrosines, enamides and enol esters that have been isolated from heterologous expression of environmental DNA (eDNA) in Escherichia coli, is reported. The synthetic libraries of N-acyl tyrosines and their 3-keto counterparts were prepared via solid-phase routes, whereas the enamides and enol esters were synthesized in solution-phase.
- Georgiades, Savvas N.,Clardy, Jon
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supporting information; experimental part
p. 3117 - 3121
(2009/04/03)
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- Luliberin analogues exhibiting a cytotoxic effect on tumor cells in vitro
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Luliberin analogues modified at the N-terminus were synthesized to search for drugs exerting a cytotoxic effect on cells of hormone-dependent tumors. A synthetic scheme effective in the preparation of analogues containing fatty acid residues was proposed. The cytotoxic effect of the peptides was studied on a number of cell lines of human tumors in vitro. The dependence of the antitumor effect on the length of peptide chain, amino acid sequence, and structure of the N-terminal group was demonstrated. Modification with palmitic acid was found to result in highly active compounds in the case of analogues containing more than ten aa, whereas modifications with lauric, caproic, or trimethylacetic acid led to compounds with significantly lower activities. Analogues of luliberin containing a palmitic acid residue and effectively inhibiting the growth of tumor cells in vitro were synthesized. Pleiades Publishing, Inc., 2006.
- Burov,Yablokova,Dorosh,Shkarubskaya,Blank,Epstein,Fridkin
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p. 413 - 419
(2008/02/11)
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- Synthetic ceramide analogues as skin permeation enhancers: Structure-Activity relationships
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The study presents new information about the structure-activity relationships of the skin permeation enhancers. A series of ceramide analogues including eight different polar head groups and six different chain lengths was synthesised. The compounds were evaluated as permeation enhancers in vitro using porcine skin. The physico-chemical parameters of the tested compounds obtained by computer modelling were used to evaluate, by multiple linear regression, the enhancement ratios (ERs) of the compounds. The regression analysis suggests that the hydrogen bonding ability of the compounds is inversely related to the ER values and that the molecular size and lipophilicity must be well balanced. In the studied enhancers having the same chain length, the enhancement activity is dependent only on their permeability coefficients. This finding confirms the Warner's hypothesis that the polar head of an enhancer is responsible for the permeation and anchoring of the molecule into the stratum corneum lipids and that it does not influence the mechanism of action. For the specific action of enhancers, that is disordering of the intercellular lipid packing, the length of the hydrophobic chain(s) and not the lipophilicity is important. Furthermore, the examination of the FTIR spectra indicated that the most active substances possess the most ordered chains. The described relationships could bring more rational approaches in designing new potent enhancers for transdermal formulations.
- Vavrova, Katerina,Hrabalek, Alexandr,Dolezal, Pavel,Samalova, Lucie,Palat, Karel,Zbytovska, Jarmila,Holas, Tomas,Klimentova, Jana
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p. 5381 - 5390
(2007/10/03)
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- Determination of N-terminal myristoylation of proteins using a combined gas chromatographic/mass spectrometric assay of derived myristoylglycine: Electron impact-induced fragmentation of acylglycine derivatives
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A method based on gas chromatography/mass spectrometry is described for the detection of N-terminal myristoylation of proteins. Myristoylglycine, derivatized as its trimethylsily (TMS) ester, gave an electron impact mass spectrum containing abundant molecular and [M - CH3]+ ions, together with several ions diagnostic of the acyl glycine moiety, namely at m/z 145, 158, 172 and 189. The compositions of these ions and the mechanism that produced them were investigated by high-resolution mass measurements, deuterium labelling and the preparation of analogons compounds. As these ions were present in the spectra of all acylglycines examined, they could be used as markers for these compounds. A selected-ion monitoring method for the detection of myristoylglycine was set up using the above ions and was used to confirm the presence of N-terminal myristoylation in three referenee peptides. A series of ions produced by radical-induced cleavage of the alkyl chain following TMS group migration and elimination of carbon dioxide gave information on the structure of the chain and could be used to determine the structure of other potential acylglycines such as those with unsaturated acyl chains. Thus the derivatives could be used not only to detect myristoylation of protein, but also to detect and determine the structures of other acyl substituents.
- McIlhinney,Harvey
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p. 900 - 910
(2007/10/02)
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- NMR investigations of the conformation of new cyclodextrin-based amphiphilic transporters for hydrophobic drugs: molecular lollipops
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Amphiphilic compounds, obtained by grafting aliphatic acids onto a modified cyclodextrin, have been synthesized and studied by solution NMR.The large chain-length dependence of the NMR spectra in aqueous media is explained by the possible formation of auto-inclusion complexes.This process has been evidenced by extensive NMR experiments and by competition with potential guests.This new class of molecules ("lollipops") provides important information for the optimization of a design for amphiphilic transporters to be included in organized phases such as micelles or liposomes.
- Bellanger, Nathalie,Perly, Bruno
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p. 215 - 226
(2007/10/02)
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- Synthesis of Acyclic Analogs of N-Acetylmuramyl-L-alanyl-D-isoglutamine (MDP)
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The synthesis of the acyclic MDP analogs 27-37 is described, the carbohydrate moiety of muramic acid being replaced by acyclic amino alcohol structures.Their preparation was accomplished by hydrolytic cleavage of the cyclic, disubstituted 3-morpholinones
- Danklmaier, Johann,Hoenig, Helmut
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p. 145 - 150
(2007/10/02)
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- A new series of amphiphilic molecules forming stable Z-type (polar) Langmuir-Blodgett films
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A new series of amphiphilic molecules bearing two amide groups along the hydrocarbon chain form head-to-tail Z-type (polar) multilayers by the Langmuir-Blodgett (LB) technique, in contrast with the common amphiphiles that tend to deposit in the head-to-he
- Popovitz-Biro,Hill,Shavit,Hung,Lahav,Leiserowitz,Sagiv,Hsiung,Meredith,Vanherzeele
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p. 2498 - 2506
(2007/10/02)
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- Synthesis and Biological Activities of N-Acetylglucosaminyl-&β(1->4)-N-Acetylmuramyl Tri- and Tetrapeptide Derivatives
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The acylated, amidated and esterified derivatives of N-acetylglucosaminyl-β(1->4)-N-acetylmuramyl tri- and tetrapeptide were synthesized and examined as to their protective effect on pseudomonal infection in the mouse and pyrogenicity in the rabbit.Modifications of the terminal end function of the peptide moieties in their molecules caused enhancement of resistance to pseudomonal infection and reduction of pyrogenicity.Among the compounds tested, sodium N-acetylglucosaminyl-β(1->4)-N-acetylmuramyl-L-alanyl-D-isoglutaminyl-(L)-stearoyl-(D)-meso-2,6-diaminopimelic acid-(D)-amide and sodium N-acetylglucosaminyl-β(1->4)-N-acetylmuramyl-L-alanyl-D-isoglutaminyl-(L)-stearoyl-(D)-meso-2,6-diaminopimelic acid-(D)-amide-(L)-D-alanine were found to be advantageous and conceivably worthwhile for further investigation as immunobiologically active compounds.
- Furuta, Rhyuji,Kawata, Shigeo,Naruto, Shunsuke,Minami, Akira,Kotani, Shozo
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p. 2561 - 2572
(2007/10/02)
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- Kasugamycin derivatives, pharmaceutical compositions and method of use
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This invention relates to new aminoglycoside derivatives and pharmaceutically acceptable salts thereof. More particularly it relates to new aminoglycoside derivatives and pharmaceutically acceptable salts thereof which have anti-viral activity, and immuno-stimulating activity and pharmaceutical compositions comprising the same. In addition, this invention also relates to methods of preparing the aminoglycoside derivatives and salts thereof.
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- Use of esters of N-hydroxysuccinimide in the synthesis of N-acylamino acids.
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Several crystalline N-hydroxysuccinimide esters of short- and long-chain fatty acids have been synthesized. These compounds react with free amino acids to form preferentially N-acylamino acids. The reaction of the N-hydroxysuccinimide esters with hydroxylamine and the behavior of the N-acylamino acids on thin-layer chromatography are described.
- Lapidot,Rappoport,Wolman
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p. 142 - 145
(2007/10/08)
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