27144-18-9Relevant academic research and scientific papers
Stabilization of polymerized vesicular systems: An application of the dynamic molecular shape concept
Wathier, Michel,Polidori, Ange,Ruiz, Karine,Fabiano, Anne-Sylvie,Pucci, Bernard
, p. 17 - 37 (2002)
A series of glycolipid surfactants derived from Tris(hydroxymethyl)acrylamidomethane (THAM) and bearing hydrocarbon or perfluorocarbon tails and an acryloyl group attached to their polar head was prepared to explore the aqueous behavior of the supramolecular systems they form. The dispersion of surfactants was achieved in water under ultrasonication conditions. Hydrocarbon compounds give heterogeneous vesicular assemblies. In the case of perfluorocarbon derivatives homogeneous vesicles were obtained. However after 1-day storage, all these systems fuse. To stabilize these vesicles, polymerization by ultra violet (UV) irradiation was carried out. During this reaction, a precipitation in water was observed for the hydrocarbon surfactants, whereas fluorocarbon structures provide stable vesicles without any alteration of their size. According to these results, the polymerization process was achieved, in the case of hydrocarbon glycolipid, in the presence of different cosurfactants bearing a single hydrocarbon tail or a polyhydroxylated head and a cholesterol terminus. In such conditions, homogeneous stable vesicles were prepared. Moreover, the THAM derived telomers bearing a cholesterol terminus were able to stabilize and reduce the size of vesicles formed with synthetic glycolipid surfactants. The drug encapsulation ability of these systems was investigated by measurement of the release kinetics of a fluorescent dye, carboxyfluorescein (CF), before and after polymerization.
A novel on-resin synthesis of C-terminally amidated peptides
Kaljuste, Kalle,Tam, James P.
, p. 9327 - 9330 (1998)
An efficient method for solid-phase synthesis of peptide alkyl- and aryl amides is developed based on cleavage of peptide-thioester linker, HS- (CH)2-CO-Nle, by a silver ion-amine complex. The metal ion-assisted acyl transfer reaction is usually completed in less than 1 h with high yields. This method is particularly suitable for preparing peptide aryl amides which are difficult to synthesize by other methods and also can be adopted for the combinatorial synthesis of nonpeptide amide libraries.
Development of cell-penetrating peptide-modified MPEG-PCL diblock copolymeric nanoparticles for systemic gene delivery
Tanaka, Ko,Kanazawa, Takanori,Shibata, Yasunori,Suda, Yumiko,Fukuda, Tsunehiko,Takashima, Yuuki,Okada, Hiroaki
, p. 229 - 238 (2010)
To develop a safe and efficient systemic non-viral gene vector, methoxy poly(ethylene glycol) (MPEG)/poly(e{open}-caprolactone) (PCL) diblock copolymers conjugated with a Tat analog through the ester or disulfide linkage were synthesized and their suitability as a systemic non-viral gene carrier evaluated. The physicochemical properties of the MPEG-PCL diblock copolymers were determined by GPC, 1H NMR and FT-IR spectroscopy. The particle sizes and in vitro (COS7 and S-180 cells) transfection efficiencies and cytotoxicity were evaluated. Furthermore, the luciferase activity was then determined in various tissues after intravenous injection of MPEG-PCL-SS-Tat/pCMV-Luc complex into mice bearing S-180 cells. The particle sizes of the MPEG-PCL-Tat copolymers with or without pDNA were about 40 and 60nm, respectively. The luciferase activity in COS7 cells transfected with pCMV-Luc with MPEG-PCL-ester-Tat or MPEG-PCL-SS-Tat was higher than that with pDNA only. MPEG-PCL-SS-Tat greatly increased the transfection efficiency compared to MPEG-PCL-ester-Tat in COS7 and S-180 cells. In an in vitro cytotoxicity test MPEG-PCL-SS-Tat did not induce any remarkable cytotoxicity. In an in vivo experiment, the synthesized MPEG-PCL-SS-Tat copolymers promoted the delivery and expression of pDNA into tumor tissue in tumor-bearing mice. In conclusion, this vector might be applicable as a tumor-targeting non-viral systemic gene carrier in the clinical setting.
“Precipitation on Nanoparticles”: Attractive Intermolecular Interactions Stabilize Specific Ligand Ratios on the Surfaces of Nanoparticles
Chu, Zonglin,Han, Yanxiao,Král, Petr,Klajn, Rafal
, p. 7023 - 7027 (2018)
Confining organic molecules to the surfaces of inorganic nanoparticles can induce intermolecular interactions between them, which can affect the composition of the mixed self-assembled monolayers obtained by co-adsorption from solution of two different molecules. Two thiolated ligands (a dialkylviologen and a zwitterionic sulfobetaine) that can interact with each other electrostatically were coadsorbed onto gold nanoparticles. The nanoparticles favor a narrow range of ratios of these two molecules that is largely independent of the molar ratio in solution. Changing the solution molar ratio of the two ligands by a factor of 5 000 affects the on-nanoparticle ratio of these ligands by only threefold. This behavior is reminiscent of the formation of insoluble inorganic salts (such as AgCl), which similarly compensate positive and negative charges upon crystallizing. Our results pave the way towards developing well-defined hybrid organic–inorganic nanostructures.
Conformational control in a photoswitchable coiled coil
Torner, Justin M.,Arora, Paramjit S.
, p. 1442 - 1445 (2021)
The coiled coil is a common protein tertiary structure intimately involved in mediating protein recognition and function. Due to their structural simplicity, coiled coils have served as attractive scaffolds for the development of functional biomaterials. Herein we describe the design of conformationally-defined coiled coil photoswitches as potential environmentally-sensitive biomaterials.
Human somatostatin receptor specificity of backbone-cyclic analogues containing novel sulfur building units
Gazal, Sharon,Gelerman, Garry,Ziv, Ofer,Karpov, Olga,Litman, Pninit,Bracha, Moshe,Afargan, Michel,Gilon, Chaim
, p. 1665 - 1671 (2002)
Somatostatin 14 (somatostatin) and its clinically available analogues octreotide, lanreotide, and vapreotide are potent inhibitors of growth hormone, insulin, and glucagon release. Recently, a novel backbone cyclic somatostatin analogue c(GABA-Phe-Trp-(D)Trp-Lys-Thr-Phe-GlyC3-NH2) (analogue 1, PTR 3173) that possesses in vivo endocrine selectivity was described. This long-acting octapeptide exhibits high affinity to human recombinant somatostatin receptors (hsst) hsst2, hsst4, and hsst5. Its novel binding profile resulted in potent in vivo inhibition of growth hormone but not of insulin release. We report the synthesis, bioactivity, and structure-activity relationship studies of compounds related to 1. In these analogues, the lactam bridge of 1 was replaced by a backbone disulfide bridge. We present a novel approach for conformational constraint of peptides by utilizing sulfur-containing building units for on-resin backbone cyclization. These disulfide backbone cyclic analogues of 1 showed significant metabolic stability as tested in various enzyme mixtures. Receptor binding assays revealed different receptor selectivity profiles for these analogues in comparison to their prototype. It was found that analogues of 1, bearing a disulfide bridge, had increased selectivity to hsst2 and hsst5; however, they exhibited weaker affinity to hsst4 as compared to 1. These studies imply that ring chemistry, ring size, and ring position of the peptide template may affect the receptor binding selectivity.
A hetero-bifunctional spacer for the smart engineering of carbon-based nanostructures
Tuci, Giulia,Luconi, Lapo,Rossin, Andrea,Baldini, Francesco,Cicchi, Stefano,Tombelli, Sara,Trono, Cosimo,Giannetti, Ambra,Manet, Ilse,Fedeli, Stefano,Brandi, Alberto,Giambastiani, Giuliano
, p. 704 - 714 (2015)
Efforts have been made in recent years to develop novel functionalisation protocols aimed at imparting multimodality and improved properties to complex carbon-based nanostructures. The incorporation of cleavable bonds to the nanomaterial surface for the controlled release (or exchange) of specific molecules under appropriate chemical and biological settings is relatively unexplored. The design and synthesis of a hetero-bifunctional linker joining a "cleavable" disulfide moiety for the covalent anchoring of a wide range of thiol end-capped (bio)molecules and a "clickable" terminal acetylene group is described. The strategy is based on the well-established copper-mediated acetylene-azide coupling reaction between the acetylene linker and single-walled carbon nanotubes decorated with phenylazido pendant arms. As a result, easily "post-derivatisable" and traceable nanostructured platforms containing a linking group potentially available for a wide range of biological probes are prepared and completely characterised.
Grid coatings for capture of proteins and other compounds
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Page/Page column 19-20, (2021/04/28)
Grids comprising a coating modified with one or more capture agents and a deactivating agent are disclosed. Methods of using such grids in connection with suitable microscopy techniques, such as for determining the structure of target compounds including proteins, are also disclosed.
Thiol- And Disulfide-Containing Vancomycin Derivatives against Bacterial Resistance and Biofilm Formation
Gademann, Karl,Shchelik, Inga S.
supporting information, p. 1898 - 1904 (2021/11/16)
Antibiotic-resistant and biofilm-associated infections constitute a rapidly growing issue. Use of the last-resort antibiotic vancomycin is under threat due to the increasing appearance of vancomycin-resistant bacteria as well as the formation of biofilms. Herein, we report a series of novel vancomycin derivatives carrying thiol- and disulfide-containing moieties. The new compounds exhibited enhanced antibacterial activity against a broad range of bacterial strains, including vancomycin-resistant microbes and Gram-negative bacteria. Moreover, all obtained derivatives demonstrated improved antibiofilm formation activity against VanB-resistant Enterococcus compared to vancomycin. This work establishes a promising strategy for combating drug-resistant bacterial infections or disrupting biofilm formation and advances the knowledge on the structural optimization of antibiotics with sulfur-containing modifications.
Multivalent dextran hybrids for efficient cytosolic delivery of biomolecular cargoes
Becker, Bastian,Englert, Simon,Schneider, Hendrik,Yanakieva, Desislava,Hofmann, Sarah,Dombrowsky, Carolin,Macarrón Palacios, Arturo,Bitsch, Sebastian,Elter, Adrian,Meckel, Tobias,Kugler, Benedikt,Schirmacher, Anastasyia,Avrutina, Olga,Diederichsen, Ulf,Kolmar, Harald
, (2021/01/20)
The development of novel biotherapeutics based on peptides and proteins is often limited to extracellular targets, because these molecules are not able to reach the cytosol. In recent years, several approaches were proposed to overcome this limitation. A plethora of cell-penetrating peptides (CPPs) was developed for cytoplasmic delivery of cell-impermeable cargo molecules. For many CPPs, multimerization or multicopy arrangement on a scaffold resulted in improved delivery but also higher cytotoxicity. Recently, we introduced dextran as multivalent, hydrophilic polysaccharide scaffold for multimerization of cell-targeting cargoes. Here, we investigated covalent conjugation of a CPP to dextran in multiple copies and assessed the ability of resulted molecular hybrid to enter the cytoplasm of mammalian cells without largely compromising cell viability. As a CPP, we used a novel, low-toxic cationic amphiphilic peptide L17E derived from M-lycotoxin. Here, we show that cell-penetrating properties of L17E are retained upon multivalent covalent linkage to dextran. Dextran-L17E efficiently mediated cytoplasmic translocation of an attached functional peptide and a peptide nucleic acid (PNA). Moreover, a synthetic route was established to mask the lysine side chains of L17E with a photolabile protecting group thus opening avenues for light-triggered activation of cellular uptake.
