- Dual system for the central nervous system targeting and blood-brain barrier transport of a selective prolyl oligopeptidase inhibitor
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Less than 2% of all potential neurotherapeutics cross the blood-brain barrier (BBB). Here, we sought to build a construct with the capacity to cross this barrier, to behave as a chemical delivery system, and, once inside the central nervous system, to be
- Teixido, Meritxell,Zurita, Esther,Mendieta, Laura,Oller-Salvia, Benjami,Prades, Roger,Tarrago, Teresa,Giralt, Ernest
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Read Online
- Photocontrolled Multidirectional Differentiation of Mesenchymal Stem Cells on an Upconversion Substrate
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The effective guidance of mesenchymal stem cell (MSC) differentiation on a substrate by near-infrared (NIR) light is particularly attractive for tissue engineering and regenerative medicine. However, most of current substrates cannot control multidirectio
- Yan, Zhengqing,Qin, Hongshuang,Ren, Jinsong,Qu, Xiaogang
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Read Online
- Dual Stimuli-Responsive Block Copolymers with Adjacent Redox- And Photo-Cleavable Linkages for Smart Drug Delivery
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A novel dual-stimuli cleavable linker containing adjacent UV light-sensitive o-nitrobenzyl ester and GSH-responsive disulfide bonds was first designed and synthesized to increase the responsivity to external stimuli. The functionalized linker was then uti
- Hsu, Chin,Liao, Zi-Xian,Lo, Yu-Lun,Soorni, Yugendhar,Tsai, Ming-Fong,Wang, Li-Fang
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Read Online
- Near-infrared upconversion controls photocaged cell adhesion
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Dynamic control of cell-surface interactions with near-infrared (NIR) light is particularly attractive for regeneration medicine and cell-based therapy. Herein we successfully achieve NIR-controlled cell adhesion with upconversion nanoparticles (UCNPs) ba
- Li, Wen,Wang, Jiasi,Ren, Jinsong,Qu, Xiaogang
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Read Online
- Photo-Cleavable Surfactants
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The present invention provides photo-cleavable anionic surfactants, particularly 4-hexylphenylazosulfonate (Azo) and sodium 4-hexylphenylazosulfonate derivatives, which can be rapidly degraded upon UV irradiation, for top-down and bottom-up proteomics. These surfactants can effectively solubilize proteins and peptide fragments with performance comparable to sodium dodecyl sulfate (SDS) and are compatible with mass spectrometry analysis of the solubilized proteins and peptide fragments. Top-down proteomic studies using the present photo-cleavable anionic surfactants has allowed the detection of 100-fold more unique proteoforms as compared to controls and has enabled the solubilization of membrane proteins for comprehensive characterization of protein post-trans-modifications. In addition, the present photo-cleavable anionic surfactants are also suitable for dissolving polypeptides in bottom-up proteomic experiments including extracellular matrix proteomics, and are suitable as a substitute for SDS in gel electrophoresis.
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Paragraph 0145; 0152-0153
(2021/08/20)
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- Non-natural amino acid and application thereof in protein site-specific modification and protein interaction
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The invention relates to a non-natural amino acid compound represented by a general formula (I) and a preparation method thereof, and applications of the non-natural amino acid compound in fixed-pointmodification of bio-macro-molecular proteins, protein i
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Paragraph 0116-0118
(2021/02/13)
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- Photo-induced multifunctional cross-linking agent, preparation method and application thereof
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The invention relates to a photo-induced multifunctional cross-linking agent as shown in a general formula (I), wherein the photo-induced multifunctional cross-linking agent is mainly applied to biomacromolecule interaction, such as protein-protein interaction and protein-nucleic acid interaction. According to the invention, the cross-linking agent can be used in biological samples or cells of cell lysis solutions to capture protein-protein interaction or protein-nucleic acid interaction, and can be applied to subsequent protein enrichment and protein cross-linking mass spectrometry; and the photo-induced multifunctional cross-linking agent has important application potential and practical value in interaction research of biomacromolecules.
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Paragraph 0155-0157
(2021/03/31)
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- O-nitrobenzyl liposomes with dual-responsive release capabilities for drug delivery
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To improve the therapeutic efficacy of anticancer drugs and reduce its toxic side effects, we synthesized a series of amphiphilic o-nitrobenzyl molecules 4-(4-N,N,N,N-dicarboxymethyl-diethylenetriamino)acetoxymethyl-3-nitro-N,N-dialk-ylbenzamide (N,N-NB-DTPA) with good photolysis property and acid sensitivity. Simultaneously, N, N-NB-DTPA liposomes composed of the o-nitrobenzyl molecules have good biocompatibility, low hemolysis rate and cytotoxicity, and the drug encapsulation efficiency of the liposomes exceeds 70%. N, N-NB-DTPA-DOX liposomes possess good stability and can keep uniform distribution in PBS solution for 10 days. The drug release rate of these drug-loaded liposomes reaches to the maximums under pH 5.0 and 30 min UV irradiation, revealing pH/UV dual-responsiveness of these drug-loaded liposomes. The low pH makes DOX separate from these drug-loaded liposomes, and the UV irradiation leads to o-nitrobenzyl ester bond cleave, which contribute to accelerate the release of drug from drug-loaded liposomes. Furthermore, N, N-NB-DTPA-DOX liposomes after UV irradiation have better therapeutic effect than single DOX·HCl, which may result from the production of nitrosobenzaldehyde derivatives after UV irradiation.
- Yao, Weihe,Liu, Chenyu,Wang, Ning,Zhou, Hengjun,Shafiq, Farishta,Yu, Simiao,Qiao, Weihong
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- PROGRAMMABLE THERMORESPONSIVE GELS
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Provided herein, inter alia, are non-crosslinked polymers that possess thermoresponsive properties. These polymers possess a cleavable bond that breaks under certain conditions The disclosure also provides pharmaceutical compositions containing the polyme
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Paragraph 0305
(2020/05/06)
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- Multi-stimuli controlled release of a transmembrane chloride ion carrier from a sulfonium-linked procarrier
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In recent times, anion transporters have received substantial consideration due to their ability to disrupt the ionic equilibrium across membrane bilayers. While numerous Cl- ion transporters were developed for channelopathies, unfortunately, poor aqueous solubility precluded their bioapplicability. Herein, we demonstrate the development of a multi-stimuli activatable anion transport approach to induce regulated transport of Cl- ions across membranes under specific conditions. The sulfonium-based procarrier was initially inactive, but the transmembrane transport of Cl- ions was activated in the presence of stimuli such as glutathione (GSH), reactive oxygen species (ROS) and light. The release of the hydrophobic anionophore from the aqueous-soluble procarrier under specific conditions leads to the successful transport of Cl- ions. Under physiological conditions, these anion carriers follow an antiport exchange mechanism to transport Cl- ions across lipid bilayers. Such multi-stimuli activatable procarriers have great potential to combat various types of channelopathies, including cancer, cystic fibrosis, kidney stones, myotonia, and others.
- Akhtar, Nasim,Biswas, Oindrila,Das, Sribash,Manna, Debasis,Patel, Anjali
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supporting information
p. 9246 - 9252
(2020/12/03)
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- Investigations into the potential role of metabolites on the anti-leukemic activity of imatinib, nilotinib and midostaurin
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The efficacy and side-effects of drugs do not just reflect the biochemical and pharmacodynamic properties of the parent compound, but often comprise of cooperative effects between the properties of the parent and active metabolites. Metabolites of imatinib, nilotinib and midostaurin have been synthesised and evaluated in assays to compare their properties as protein kinase inhibitors with the parent drugs. The N-desmethylmetabolite of imatinib is substantially less active than imatinib as a BCR-ABL1 kinase inhibitor, thus providing an explanation as to why patients producing high levels of this metabolite show a relatively low response rate in chronic myeloid leukaemia (CML) treatment. The hydroxymethylphenyl and N-oxide metabolites of imatinib and nilotinib are only weakly active as BCR-ABL1 inhibitors and are unlikely to play a role in the efficacy of either drug in CML. The 3-(R)-HO-metabolite of midostaurin shows appreciable accumulation following chronic drug administration and, in addition to mutant forms of FLT3, potently inhibits the PDPK1 and VEGFR2 kinases (IC50 values 100 nM), suggesting that it might contribute to drug efficacy in acute myeloid leukaemia patients. The case studies discussed here provide further examples of how the synthesis and characterisation of metabolites can make important contributions to understanding the clinical efficacy of drugs.
- Manley, Paul W.
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p. 561 - 570
(2019/09/03)
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- Preparation method of near-infrared light-controlled visual medicine carrier
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The invention discloses a near-infrared light-controlled medicine carrier, namely a carrier with medicine carrying ability which is formed by o-nitrobenzyl ester amphiphilic molecule vesicles encapsulating water-soluble upconversion nanoparticles (Ligand-UCNPs), and belongs to the field of surfactants. The total number of alkyl carbon atoms of a fatty chain is 6 to 36. A preparation method of thecarrier comprises the following three steps of synthesizing oil-soluble upconversion nanoparticles (OA-UCNPs); synthesizing the water-soluble upconversion nanoparticles (Ligand-UCNPs); encapsulatingthe upconversion nanoparticles by the o-nitrobenzyl ester amphiphilic molecules. The near-infrared light-controlled medicine carrier has the advantages that the o-nitrobenzyl ester amphiphilic molecules have ultraviolet light crackability; by introducing the upconversion nanoparticles (UCNPs) which have large tissue penetration depth and can convert the near-infrared light with little injury to ahuman body into the ultraviolet light, the defects of small penetration depth and large injury to the human body of the ultraviolet light are overcome, and the purpose of medicine release by photolysis is realized; the near-infrared light-controlled medicine carrier is a potential near-infrared light-controlled medicine release carrier.
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Paragraph 0073-0075
(2019/09/17)
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- Constrained and UV-activatable cell-penetrating peptides for intracellular delivery of liposomes
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Herein we report on the development of a novel method of constraining a cell-penetrating peptide, which can be used to trigger transport of liposomes into cells upon in this case radiation with UV-light. A cell-penetrating peptide, which was modified on b
- Hansen, Morten B.,Van Gaal, Ethlinn,Minten, Inge,Storm, Gert,Van Hest, Jan C.M.,Loewik, Dennis W.P.M.
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- Radiation sensitive self-assembled monolayers and uses thereof
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The invention is directed to a radiation sensitive compound comprising a surface binding group proximate to one end of the compound for attachment to a substrate, and a metal binding group proximate to an opposite end of the compound. The metal binding gr
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Page/Page column 11-12
(2012/10/07)
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- Design and synthesis of lipids for the fabrication of functional lipidic cubic-phase biomaterials
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A series of novel lipids with designed functionalities were synthesized. These lipids are based on conjugation of α-amino acids and their esters, cationic, anionic, neutral, and photochromic moieties to the lipophilic 9-cis octadecenyl chains by amide, ester, thioester, or amine bonds. Because of the plasticity of lipidic cubic phases, it is envisaged that when mixed with monooleoyl-rac-glycerol (monoolein, MO) and water at appropriate proportions, they would assemble to form bicontinuous lipidic cubic phases (LCPs) that exhibit the well-known material properties of LCPs such as phase stability, optical transparency, and chemical permeability. Moreover, due to the nature and position of the functionality at the headgroup region, we envision them to perform as functional materials by design.
- Osornio, Yazmin M.,Uebelhart, Peter,Bosshard, Silvan,Konrad, Fabian,Siegel, Jay S.,Landau, Ehud M.
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p. 10583 - 10595
(2013/02/22)
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- Synthesis and evaluation of the anti parasitic activity of aromatic nitro compounds
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A series of nitroaromatic compounds was synthesized and evaluated as potential antileishmanial and trypanocidal agents. Five compounds exerted significant anti-leishmanial activity in vitro against promastigotes forms of Leishmania (L.) amazonensis, with
- Lopes, Marcela S.,De Souza Pietra, Renata C.C.,Borgati, Tatiane F.,Romeiro, Carla F.D.,Júnior, Policarpo A.S.,Romanha, Alvaro J.,Alves, Ricardo J.,Souza-Fagundes, Elaine M.,Fernandes, Ana Paula S.M.,De Oliveira, Renata B.
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scheme or table
p. 5443 - 5447
(2011/12/15)
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- COMPOUNDS THAT ACT AS A VEHICLE FOR DELIVERY THROUGH THE BLOOD-BRAIN BARRIER AND CHARGE DELIVERY VEHICLE CONSTRUCTIONS
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Compounds of formula (I), where R1 and R3 are H or (C1-C4)-alkyl; R2 is H or a C-radical derived from one of the known ring systems with 1-4 rings; X1 is a (C1-C6)-alk
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Page/Page column 4 -5
(2010/02/17)
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- Diketopiperazines as a tool for the study of transport across the Blood-Brain Barrier (BBB) and their potential use as BBB-shuttles
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Here we prepared and evaluated two libraries of mono-N-methylated and di-N-methylated diketopiperazines (DKPs) by parallel artificial membrane permeability assay and immobilized artificial membrane chromatography in order to obtain information on the features that govern the passage of peptidic molecules across the blood-brain barrier (BBB) by passive diffusion. On the basis of the results from these two libraries, we prepared and evaluated several DKP-baicalin and DKP-dopamine constructs. The DKPs or cyclic dipeptide scaffolds can be considered a novel family of brain delivery systems (BBB-shuttles) to transport to the brain drugs and other cargos that cannot cross the BBB unaided.
- Teixido, Meritxell,Zurita, Esther,Malakoutikhah, Morteza,Tarrago, Teresa,Giralt, Ernest
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p. 11802 - 11813
(2008/03/27)
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- Syntheses and Activities of New C10 β-Turn Peptidomimetics
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A program to identify small molecules that mimic or disrupt protein-protein interactions led us to design the peptidomimetics 1-3. Solid-phase syntheses of 1-3 were developed. The purities of the crude materials isolated from the resin tend to be highest for the S- and N-compounds 2 and 3 and better than in the corresponding syntheses of peptidomimetics A. The particular dipeptide units incorporated were chosen to correspond with the turn regions of the neurotrophins (e.g., nerve growth factor {NGF} and the neurotrophin factor-3 {NT-3}). Preliminary studies were performed to access the binding of these analogues to Trk receptors and their ability to induce cell survival (just as NGF and NT-3 do). Several active compounds were identified. However, poor water solubilities of some of the other compounds preclude reliable testing. Consequently, solid-phase modifications to the synthetic procedures were investigated to provide access to the derivatives 12-14 in which the aromatic nitro group is replaced by amine, guanidine, or sulfonamide functionalities. The latter are more acceptable pharmacophores than nitro groups and also tend to increase the water solubilities of the peptidomimetics.
- Lee, Hong Boon,Zaccaro, Maria Clara,Pattarawarapan, Mookda,Roy, Sudipta,Saragovi, H. Uri,Burgess, Kevin
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p. 701 - 713
(2007/10/03)
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- A ribozyme with michaelase activity: synthesis of the substrate precursors.
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The ability to generate RNA molecules that can catalyze complex organic transformations not only facilitates the reconstruction and plausibility of possible prebiotic reaction pathways but is also crucial for elucidating the potential of the application of RNA catalysts in organic syntheses. Iterative RNA selection previously identified a ribozyme that catalyzes the Michael addition of a cysteine thiol to an alpha,beta-unsaturated amide. This reaction is chemically similar to the rate limiting step of the thymidylate synthase reaction, which is the corresponding reaction of a cysteine thiol to the double-bond of the uracil nucleobase. Here we provide a detailed description of the synthesis of the ribozyme substrates and the substrate oligonucleotides used for its characterization and the investigation of the background reaction. We also describe the further characterization of the ribozyme with respect to substrate specificity. We show that the thiol group of the cysteine nucleophile is essential for the reaction to proceed. When substituted for a thiomethyl group, no reaction takes place.
- Eisenfuehr, Alexander,Arora, Paramjit S,Sengle, Gerhard,Takaoka, Leo R,Nowick, James S,Famulok, Michael
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p. 235 - 249
(2007/10/03)
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- Radical and palladium-mediated cyclizations of ortho-iodo benzyl enamines: A scope and limitation study
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Radical and palladium-mediated cyclizations of ortho-iodo benzyl enamines were compared to determine their potential application to the synthesis of libraries of compounds on solid support.
- Berteina, Sabine,De Mesmaeker, Alain
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p. 1227 - 1230
(2007/10/03)
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- The use of the Nbb-resin for the solid-phase synthesis of peptide alkylesters and alkylamides. Synthesis of leuprolide
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The use of nucleophiles for the cleavage of an o-nitrobenzylester peptide-resin bond in order to afford peptide alkylesters and alkylamides has been studied. With this purpose, three short peptide sequences anchored to a Nbb-resin were used as models. Pep
- Nicolas, Ernesto,Clemente, Javier,Ferrer, Tina,Albericio, Fernando,Giralt, Ernest
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p. 3179 - 3194
(2007/10/03)
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- Convergent solid-phase peptide synthesis. X. Synthesis and purification of protected peptide fragments using the photolabile Nbb-resin
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Protected peptide fragments corresponding to the 12-18, 31-38 and 59-67 segments of the Uteroglobin monomer have been synthesised on a solid support using the photolabile ortho-nitrobenzyl unit as a handle. Attachment of the first amino acid of the sequen
- Lloyd-Williams, Paul,Gairi, Margarida,Albericio, Fernando,Giralt, Ernest
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p. 9867 - 9880
(2007/10/02)
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- ENZYMIC SYNTHESIS OF OLIGOSACCHARIDES ON A POLYMER SUPPORT. LIGHT-SENSITIVE, SUBSTITUTED POLYACRYLAMIDE BEADS
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Two light-sensitive, gluco and cellobio polimers, were synthesized by formation of an amide bond between 4-carboxy-2-nitrobenzyl β-D-glucopyranoside or 4-carboxy-2-nitrobenzyl 4-O-β-D-glucopyranosyl-β-D-glucopyranoside, respectively, and aminoethyl substi
- Zehavi, Uri,Sadeh, Shoshana,Herchman, Mina
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