- Naloxegol Oxalate and Solid Dispersion thereof
-
The present invention relates to solid dispersion of Naloxegol oxalate. Further, the present invention relates to an improved process for Naloxegol oxalate and intermediates thereof.
- -
-
Paragraph 0126
(2021/11/05)
-
- Effects of 18F-fluorinated neopentyl glycol side-chain on the biological characteristics of stilbene amyloid-β PET ligands
-
Introduction: The 2,2-dihydroxymethyl-1-[18F]fluoropropane group, also called 18F-labelled neopentyl glycol side-chain, is a novel 18F-labelling group for positron emission tomography (PET) imaging agents. The aim of using this group is to develop simple purification with solid-phase extraction without high-performance liquid chromatography. However, the effects of the neopentyl 18F-labelling group on the characteristics of brain imaging agents are unknown. Here, we added this side-chain to compounds with an aminostilbene structure to evaluate their effects on the biological properties of aminostilbene as an amyloid-β (Aβ) radioligand. Methods: Biodistributions of four novel 18F-labelled stilbene compounds with different lengths of polyethylene glycol (PEG) linkers, called [18F]Cpd-0, -1, -2, and -4, (PEG = 0, 1, 2, and 4), and [18F]AV-1 in normal mice were evaluated. Metabolite analysis of [18F]Cpd-0 and -1 was performed with mouse plasma and brain. A competitive binding assay of [18F]AV-1 binding to Aβ1–42 fibrils was performed to determine the binding properties of the compounds. Results: [18F]Cpd-0, -1, and -2 demonstrated moderate initial brain uptake in mice (3.1–4.2% injected dose/g at 2 min post-injection) followed by fast clearance, and in vivo defluorination of these compounds was negligible. [18F]Cpd-4 exhibited low brain uptake and high bone uptake. Compared with [18F]Cpd-1, the percentage of [18F]Cpd-0 in mouse brain was high at 10 min post-injection. A competitive binding assay revealed partial interference effects by the neopentyl glycol side-chain on binding of stilbene compounds to Aβ1–42 fibrils. Conclusions: Aminostilbene compounds with two or fewer PEG linkers containing an 18F-labelled neopentyl glycol side-chain demonstrated preferable pharmacokinetic properties as a brain imaging radioligand in normal mice. These side-chains can be used as an alternative labelling group for imaging agents targeting the brain.
- Tago, Tetsuro,Toyohara, Jun,Fujimaki, Ryo,Tatsuta, Maho,Song, Ruichong,Hirano, Keiichi,Iwai, Kumiko,Tanaka, Hiroshi
-
-
- Optimization of IEDDA bioorthogonal system: Efficient process to improve trans-cyclooctene/tetrazine interaction
-
The antibody pretargeting approach for radioimmunotherapy (RIT) using inverse electron demand Diels-Alder cycloaddition (IEDDA) constitutes an emerging theranostic approach for solid cancers. However, IEDDA pretargeting has not reached clinical trial. The major limitation of the IEDDA strategy depends largely on trans-cyclooctene (TCO) stability. Indeed, TCO may isomerize into the more stable but unreactive cis-cyclooctene (CCO), leading to a drastic decrease of IEDDA efficiency. We have thus developed both efficient and reproducible synthetic pathways and analytical follow up for (PEGylated) TCO derivatives, providing high TCO isomeric purity for antibody modification. We have set up an original process to limit the isomerization of TCO to CCO before the mAbs’ functionalization to allow high TCO/tetrazine cycloaddition.
- Béquignat, Jean-Baptiste,Boucheix, Claude,Canitrot, Damien,Chezal, Jean-Michel,Degoul, Fran?oise,Miot-Noirault, Elisabeth,Moreau, Emmanuel,Navarro-Teulon, Isabelle,Quintana, Mercedes,Rondon, Aurélie,Taiariol, Ludivine,Ty, Nancy
-
supporting information
(2020/07/21)
-
- PROTEOLYSIS-TARGETING PROTACS INDUCING DEGRADATION OF C-MIC PROTEIN
-
Disclosed are proteolysis-targeting chimeric molecules (PROTACs) that induce degradation of c-MYC protein. The disclosed PROTACs typically include a first targeting moiety that binds to c-MYC (MC-MYC) which may be derived from a substituted heterocycle that binds to c-MYC such as a substituted pyrazole. The first targeting moiety typically is linked via a bond or a linker (L) to a second targeting moiety that binds to an E3 ubiquitin ligase (ME3). AS such, the disclosed PROTACS may be described as having a formula Mc-MYC-L-ME3 or ME3-L-Mc-MYC.
- -
-
Page/Page column 00205-00206; 00209-00210
(2020/12/30)
-
- SUPRAMOLECULAR PROTEIN ASSEMBLIES WITH ADVANCED FUNCTIONS AND SYNTHESIS THEREOF
-
The present invention discloses stimuli-sensitive protein conjugate which can make supramolecular protein assemblies and methods for using the same. The present invention provides simple and rational process for construction of said stimuli-sensitive spherical protein assemblies through supramolecular chemical strategy.
- -
-
Paragraph 0462-0463
(2019/05/18)
-
- IRAK DEGRADERS AND USES THEREOF
-
The present invention provides compounds, compositions thereof, and methods of using the same.
- -
-
Paragraph 1988; 1989
(2019/07/10)
-
- NALOXEGOL OXALATE AND SOLID DISPERSION THEREOF
-
The present invention relates to solid dispersion of Naloxegol oxalate. Further, the present invention relates to an improved process for Naloxegol oxalate and intermediates thereof.
- -
-
Paragraph 24; 25
(2018/06/12)
-
- EGFR PROTEOLYSIS TARGETING CHIMERIC MOLECULES AND ASSOCIATED METHODS OF USE
-
The present disclosure relates to bifunctional compounds, which find utility as modulators of receptor tyrosine kinase (RTK) proteins. In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a ligand which binds to an E3 ubiquitin ligase and on the other end a moiety which binds a target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effectuate ubiquitination, and therefore, degradation (and inhibition) of the target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.
- -
-
Paragraph 00661; 00662
(2018/07/29)
-
- TAU-PROTEIN TARGETING PROTACS AND ASSOCIATED METHODS OF USE
-
The present disclosure relates to bifunctional compounds, which find utility as modulators of tau protein. In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a VHL or cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds tau protein, such that tau protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of tau. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of tau protein. Diseases or disorders that result from aggregation or accumulation of tau protein are treated or prevented with compounds and compositions of the present disclosure.
- -
-
Paragraph 1451
(2018/05/24)
-
- Templated Formation of Luminescent Virus-like Particles by Tailor-Made Pt(II) Amphiphiles
-
Virus-like particles (VLPs) have been created from luminescent Pt(II) complex amphiphiles, able to form supramolecular structures in water solutions, that can be encapsulated or act as templates of cowpea chlorotic mottle virus capsid proteins. By virtue
- Sinn, Stephan,Yang, Liulin,Biedermann, Frank,Wang, Di,Kübel, Christian,Cornelissen, Jeroen J. L. M.,De Cola, Luisa
-
supporting information
p. 2355 - 2362
(2018/02/19)
-
- Solid Phase Stepwise Synthesis of Polyethylene Glycols
-
Polyethylene glycol (PEG) and derivatives with eight and twelve ethylene glycol units were synthesized by stepwise addition of tetraethylene glycol monomers on a polystyrene solid support. The monomer contains a tosyl group at one end and a dimethoxytrityl group at the other. The Wang resin, which contains the 4-benzyloxy benzyl alcohol function, was used as the support. The synthetic cycle consists of deprotonation, Williamson ether formation (coupling), and detritylation. Cleavage of PEGs from solid support was achieved with trifluoroacetic acid. The synthesis including monomer synthesis was entirely chromatography-free. PEG products including those with different functionalities at the two termini were obtained in high yields. The products were analyzed with ESI and MALDI-TOF MS and were found close to monodispersity.
- Khanal, Ashok,Fang, Shiyue
-
supporting information
p. 15133 - 15142
(2017/10/31)
-
- Anion-Selective Cholesterol Decorated Macrocyclic Transmembrane Ion Carriers
-
Anion transporters play a vital role in cellular processes and their dysregulation leads to a range of diseases such as cystic fibrosis, Bartter's syndrome and epilepsy. Synthetic chloride transporters are known to induce apoptosis in cancer cell lines. Herein, we report triamide macrocycles that are easily synthesized and externally functionalized by pendant membrane-permeable groups. Among a variety of chains appended onto the macrocycle scaffold, cholesterol is found to be the best with an EC50 value of 0.44 μM. The macrocycle is highly anion-selective and transports ions via an OH-/X- antiport mechanism. The macrocycle is an interesting scaffold for ion-Transport as it is able to discriminate between various anions and shows a preference for SCN- and Cl-. Such anion-selective transporters are highly attractive model systems to study ion-Transport mechanisms and could potentially be of high therapeutic value.
- Behera, Harekrushna,Madhavan, Nandita
-
supporting information
p. 12919 - 12922
(2017/09/26)
-
- COMPOUNDS FOR THE MODULATION OF RIP2 KINASE ACTIVITY
-
The present invention relates to compounds, compositions, combinations and medicaments containing said compounds and processes for their preparation. The invention also relates to the use of said compounds, combinations, compositions and medicaments, for example as inhibitors of the activity of RIP2 kinase, including degrading RIP2 kinase, the treatment of diseases and conditions mediated by the RIP2 kinase, in particular for the treatment of inflammatory diseases or conditions.
- -
-
Page/Page column 52; 53
(2017/04/11)
-
- Precursor for preparing micelle
-
The present invention refers to linker, polar material and two aliphatic hydrocarbon chain comprised of precursor for micellar formation, said precursor manufacturing method, including micelles and including said precursor of said micelle relates to drug delivery. In the present invention number the use of precursor for forming micelle under public affairs, two game machine included in same, non-polar tail due to, than micelles of the existing method a relatively high stability of the insertion part and the holder under trillion number micelle, micelles including drug delivery or the like and can be widely used for the development of.. (by machine translation)
- -
-
Paragraph 0165; 0166
(2016/11/21)
-
- A large ring sulfate and its preparation method and application
-
The invention relates to novel macrocyclic cyclic sulfate, and a preparation method and application thereof. The novel macrocyclic cyclic sulfate comprises macrocyclic cyclic sulfite and macrocyclic cyclic sulfate, wherein the structures of the macrocyclic cyclic sulfite and the macrocyclic cyclic sulfate are shown in a formula I and a formula II respectively; X and Y are respectively or jointly alkane, olefin, oxo-alkane, thio-alkane or aza-alkane and the like, with the total atom number being more than 4, on a ring-forming shortest chain. The macrocyclic cyclic sulfite is obtained by cyclizing a long-chain glycol compound by using thionyl chloride under the action of alkali; the macrocyclic cyclic sulfate is obtained through oxidation under metal catalysis; various derivatives of the long-chain glycol can be obtained through ring-opening reaction. The macrocyclic cyclic sulfate provided by the invention has a novel structure, can serve as an important organic synthesis intermediate, are abundant in raw material source, low in cost, mild in preparation condition, high in yield and easy to operate, can simplify the synthesis route of a large amount of chemical raw materials and medical intermediates, and has an important application prospect.
- -
-
Paragraph 0070; 0071; 0072
(2017/02/17)
-
- Towards potential nanoparticle contrast agents: Synthesis of new functionalized PEG bisphosphonates
-
The use of nanotechnologies for biomedical applications took a real development during these last years. To allow an effective targeting for biomedical imaging applications, the adsorption of plasmatic proteins on the surface of nanoparticles must be prevented to reduce the hepatic capture and increase the plasmatic time life. In biologic media, metal oxide nanoparticles are not stable and must be coated by biocompatible organic ligands. The use of phosphonate ligands to modify the nanoparticle surface drew a lot of attention in the last years for the design of highly functional hybrid materials. Here, we report a methodology to synthesize bisphosphonates having functionalized PEG side chains with different lengths. The key step is a procedure developed in our laboratory to introduce the bisphosphonate from acyl chloride and tris(trimethylsilyl)phosphite in one step.
- Kachbi-Khelfallah, Souad,Monteil, Maelle,Cortes-Clerget, Margery,Migianu-Griffoni, Evelyne,Pirat, Jean-Luc,Gager, Olivier,Deschamp, Julia,Lecouvey, Marc
-
supporting information
p. 1366 - 1370
(2016/08/02)
-
- Perfluoroalkylated poly(oxyethylene) thiols: Synthesis, adsorption dynamics and surface activity at the air/water interface, and bubble stabilization behaviour
-
We report the synthesis of four new perfluoroalkylated thiols, CnF2n+1(CH2)2(OCH2CH2)ySH (FnH2(OE)y with n = 4 and 6; y = 4 and 6, that have a hydrophilic poly(oxyethylene) (POE) segment inserted between the hydrophobic fluorinated chain and the thiol functional group. The dynamics of adsorption and surface activity of these compounds at the air/water interface were studied using bubble profile analysis tensiometry. The adsorption kinetics profiles show that all compounds diffuse rapidly to the air/water interface and decrease the interfacial tension of water to values ranging from 16.5 to 31.6 mN m-1, which qualifies them as potential components of microbubble shells. Their ability to self-assemble and stabilize gaseous microbubbles in the presence or absence of a fluorocarbon gas (perfluorohexane) was investigated by optical microscopy. Three out of the four compounds (the two F6 derivatives and F4H2(OE)6) were able to form and stabilize microbubbles. Microbubbles based on both F6 PEG thiols are more stable than those based on the F4 derivative. The number of oxyethylene (OE) groups substantially influences bubble stability; the higher the number of OEs, the more stable the microbubbles. Finally, the most important stabilising effect was obtained by introducing an internal fluorocarbon gas, whose presence in the bubble increases bubble stability from 6 h to 5 days for the most promising candidate, F6H2(OE)6SH.
- Polavarapu, Prasad,Krafft, Marie Pierre
-
-
- Development of a Scalable Process for α-Amino-ω-methoxyl-dodecaethylene Glycol
-
We have developed a process for the efficient and scalable preparation of heterofunctionalized dodecaethylene glycol from the readily available tetraethylene glycol and its macrocyclic sulfate. By employing the benzyl group as both a protecting group and a separative tag, multiple chromatographic separations were avoided. With this method, α-amino-ω-methyl-dodecaethylene glycol was prepared on a 53 g scale with high purity and 61% overall yield in eight steps and one chromatographic separation.
- Xia, Guiquan,Li, Yu,Yang, Zhigang,Jiang, Zhong-Xing
-
p. 1769 - 1773
(2015/12/01)
-
- Highly efficient synthesis of monodisperse poly(ethylene glycols) and derivatives through macrocyclization of oligo(ethylene glycols)
-
A macrocyclic sulfate (MCS)-based approach to monodisperse poly(ethylene glycols) (M-PEGs) and their monofunctionalized derivatives has been developed. Macrocyclization of oligo(ethylene glycols) (OEGs) provides MCS (up to a 62-membered macrocycle) as versatile precursors for a range of monofunctionalized M-PEGs. Through iterative nucleophilic ring-opening reactions of MCS without performing group protection and activation, a series of M-PEGs, including the unprecedented 64-mer (2850Da), can be readily prepared. Synthetic simplicity coupled with versatility of this new strategy may pave the way for broader applications of M-PEGs. Macrocycles make synthesis easier: Convenient macrocyclization of the OEGs provides versatile macrocyclic sulfates. These compounds are cornerstones for both monofunctionalization of OEGs and highly efficient synthesis of monodisperse PEGs and derivatives, including an unprecedented 64-mer.
- Zhang, Hua,Li, Xuefei,Shi, Qiuyan,Li, Yu,Xia, Guiquan,Chen, Long,Yang, Zhigang,Jiang, Zhong-Xing
-
p. 3763 - 3767
(2015/03/18)
-
- 99mTc Radiolabeling and Biological Evaluation of Nanoparticles Functionalized with a Versatile Coating Ligand
-
Radiolabeling allows noninvasive imaging by single photon emission computed tomography (SPECT) or positron emission tomography (PET) for assessing the biodistribution of nanostructures. Herein, the synthesis of a new coating ligand for gold nanoparticles (AuNPs) and quantum dots (QDs) is reported. This ligand is multifunctional; it combines the metal chelate with conjugating functions to biological vectors. The concept allows the coupling of any targeting function to the chelator; an example for the prostate specific membrane antigen is given. Derivatized NPs can directly be labeled in one step with [99mTc(OH2)3(CO)3]+. AuNPs in particular are highly stable, a prerequisite for in vivo studies excluding misinterpretation of the biodistribution data. AuNPs with differing sizes (7 and 14 nm core diameter) were administered intravenously into nude NMRI mice bearing LNCaP xenografts. MicroSPECT images show for both probes rapid clearance from the blood pool through the hepatobiliary pathway. The 7 nm AuNPs revealed a significantly higher bone uptake than the 14 nm AuNPs. The high affinity towards bone mineral is further confirmed in vitro with hydroxyapatite.
- Felber, Michael,Bauwens, Matthias,Mateos, José M.,Imstepf, Sebastian,Mottaghy, Felix M.,Alberto, Roger
-
supporting information
p. 6090 - 6099
(2015/04/14)
-
- 8034
-
Abstract A series of arabinose glycosyl sulfamides with varying alkyl chain types and lengths were synthesised as mimics of decaprenolphosphoarabinose (DPA), and as potential inhibitors of mycobacterial cell wall biosynthesis. Unprecedented conversion of
- Suthagar, Kajitha,Watson, Andrew J.A.,Wilkinson, Brendan L.,Fairbanks, Antony J.
-
p. 153 - 166
(2015/08/24)
-
- A molecular Fe-complex as a catalyst probe for in-gel visual detection of proteins via signal amplification
-
We report the use of a molecular peroxidase mimic biuret-Fe-TAML for chemoselective labeling of proteins and the subsequent visual detection (0.1 pmoles) of the conjugate in a polyacrylamide gel by catalytic signal amplification. Use of this probe in act
- Kumari, Sushma,Panda, Chakadola,Mazumdar, Shyamalava,Sen Gupta, Sayam
-
supporting information
p. 15257 - 15260
(2015/10/20)
-
- Synthesis of poly(ethylene oxide) approaching monodispersity
-
Polydispersity in polymers hinders fundamental understanding of their structure-property relationships and prevents them from being used in fields like medicine, where polydispersity affects biological activity. The polydispersity of relatively short-chain poly(ethylene oxide) [(CH 2CH2O2)n; PEO] affects its biological activity, for example, the toxicity and efficacy of PEOylated drugs. As a result, there have been intensive efforts to reduce the dispersity as much as possible (truly monodispersed materials are not possible). Here we report a synthetic procedure that leads to an unprecedented low level of dispersity. We also show for the first time that it is possible to discriminate between PEOs differing in only 1 ethylene oxide (EO) unit, essential in order to verify the exceptionally low levels of dispersity achieved here. It is anticipated that the synthesis of poly(ethylene oxide) approaching monodispersity will be of value in many fields where the applications are sensitive to the distribution of molar mass.
- Maranski, Krzysztof,Andreev, Yuri G.,Bruce, Peter G.
-
supporting information
p. 6411 - 6413
(2014/06/24)
-
- Synthesis of a library of propargylated and PEGylated α-hydroxy acids toward "clickable" polylactides via hydrolysis of cyanohydrin derivatives
-
A new simple and practical protocol for scalable synthesis of a novel library of propargylated and PEGylated α-hydroxy acids toward the preparation of "clickable" polylactides was described. The overall synthesis starting from readily available propargyl alcohol, bromoacetaldehyde diethyl acetal, and OEGs or PEGs was developed as a convenient procedure with low cost and no need of column chromatographic purification. The terminal alkyne functionality survives from hydrolysis of the corresponding easily accessible cyanohydrin derivatives in methanolic sulfuric acid. Facile desymmetrization, monofunctionalization, and efficient chain-elongation coupling of OEGs further enable the incorporation of OEGs to α-hydroxy acids in a simple and efficient manner. At the end, synthesis of allyloxy lactic acid indicates that an alkene group is also compatible with the developed method. (Chemical Equation Presented).
- Zhang, Quanxuan,Ren, Hong,Baker, Gregory L.
-
p. 9546 - 9555
(2015/02/19)
-
- Propargylamine-isothiocyanate reaction: Efficient conjugation chemistry in aqueous media
-
A coupling reaction between secondary propargyl amines and isothiocyanates in aqueous media is described. The reaction is high-yielding and affords cyclized products within 2-24 h. A functionalized ether lipid was synthesized in 8 steps, formulated as liposomes with POPC and conjugated to FITC under mild conditions using this method. This journal is the Partner Organisations 2014.
- Viart,Larsen,Tassone,Andresen,Clausen
-
supporting information
p. 7800 - 7802
(2014/07/08)
-
- A practical and scalable process to selectively monofunctionalize water-soluble α,ω-diols
-
A practical protocol for rapid and scalable synthesis of monofunctionalized α,ω-diols using a simple and inexpensive THP ether protection/deprotection strategy was described. Use of inexpensive DHP source and ease to remove excess water-soluble α,ω-diols
- Zhang, Quanxuan,Ren, Hong,Baker, Gregory L.
-
supporting information
p. 3384 - 3386
(2014/06/09)
-
- An improved synthesis of a fluorophosphonate-polyethylene glycol-biotin probe and its use against competitive substrates
-
The fluorophosphonate (FP) moiety attached to a biotin tag is a prototype chemical probe used to quantitatively analyze and enrich active serine hydrolases in complex proteomes in an approach called activity-based protein profiling (ABPP). In this study we have designed a novel synthetic route to a known FP probe linked by polyethylene glycol to a biotin tag (FP-PEG-biotin). Our route markedly increases the efficiency of the probe synthesis and overcomes several problems of a prior synthesis. As a proof of principle, FP-PEG-biotin was evaluated against isolated protein mixtures and different rat-tissue homogenates, showing its ability to specifically target serine hydrolases. We also assessed the ability of FP-PEG-biotin to compete with substrates that have high enzyme turnover rates. The reduced protein-band intensities resulting in these competition studies demonstrate a new application of FP-based probes seldom explored before.
- Xu, Hao,Sabit, Hairat,Amidon, Gordon L.,Showalter, H.D. Hollis
-
-
- Synthesis of gemini surfactants with twelve symmetric fluorine atoms and one singlet 19F MR signal as novel 19F MRI agents
-
A family of fluorinated gemini surfactants derived from perfluoropinacol has been synthesized as novel 19F magnetic resonance imaging ( 19F MRI) agents. These fluorinated surfactants with 12 symmetric fluorine atoms and one singlet
- Li, Yu,Thapa, Bijaya,Zhang, Hua,Li, Xuefei,Yu, Fanghua,Jeong, Eun-Kee,Yang, Zhigang,Jiang, Zhong-Xing
-
supporting information
p. 9586 - 9590
(2013/10/22)
-
- DENDRIMERS AND METHODS OF PREPARING SAME THROUGH PROPORTIONATE BRANCHING
-
The present invention provides for monodispersed dendrimers having a core, branches and periphery ends, wherein the number of branches increases exponentially from the core to the periphery end and the length of the branches increases exponentially from t
- -
-
Paragraph 0092
(2013/08/14)
-
- Supramolecular polymerization in water harnessing both hydrophobic effects and hydrogen bond formation
-
The formation of supramolecular polymers in water through rational design of a benzene-1,3,5-tricarboxamide (BTA) motif is presented. Intermolecular hydrogen bonding and hydrophobic effects cooperate in the self-assembly into long fibrillar aggregates. Minimal changes in molecular structure significantly affect the internal packing of the aggregates. The Royal Society of Chemistry 2013.
- Leenders, Christianus M. A.,Albertazzi, Lorenzo,Mes, Tristan,Koenigs, Marcel M. E.,Palmans, Anja R. A.,Meijer
-
supporting information
p. 1963 - 1965
(2013/04/10)
-
- Avoiding steric congestion in dendrimer growth through proportionate branching: A twist on da Vincis rule of tree branching
-
Making defect-free macromolecules is a challenging issue in chemical synthesis. This challenge is especially pronounced in dendrimer synthesis where exponential growth quickly leads to steric congestion. To overcome this difficulty, proportionate branchin
- Yue, Xuyi,Taraban, Marc B.,Hyland, Laura L.,Yu, Yihua Bruce
-
p. 8879 - 8887
(2013/01/15)
-
- Application of a water-soluble pyridyl disulfide amine linker for use in Cu-free click bioconjugation
-
Described herein is the design and synthesis of a discrete heterobifunctional PEG-based pyridyl disulfide/amine-containing linker that can be used in the Cu-free click preparation of bioconjugates. The title PEG-based pyridyl disulfide amine linker is a potentially useful reagent for preparing water-soluble disulfide-linked cargos, and that it may be particularly valuable in expanding the field of Cu-free click-based bioconjugations to include reductively labile antibody, polymer, or nanoparticle-based drug conjugates.
- Thomas, Joshua D.,Burke Jr., Terrence R.
-
scheme or table
p. 4316 - 4319
(2011/09/12)
-
- High-purity discrete PEG-oligomer crystals allow structural insight
-
To great (monodisperse) lengths: An improved synthesis of purer ethylene glycol (EG) oligomers allows access to 16- and 32-mers pure enough for multiple incorporation, and also to the longest (48-mer) discrete EG oligomer yet reported. The high purity enables the first crystallizations and hence the first glimpses of secondary 310-helical PEG structures.
- French, Alister C.,Thompson, Amber L.,Davis, Benjamin G.
-
supporting information; experimental part
p. 1248 - 1252
(2009/06/30)
-
- Bna Conjugates and Methods of Use
-
Modified natriuretic compounds and conjugates thereof are disclosed in the present invention. In particular, conjugated forms of hBNP are provided that include at least one modifying moiety attached thereto. The modified natriuretic compound conjugates retain activity for stimulating cGMP production, binding to NPR-A receptor, decreasing arterial blood pressure and in some embodiments an improved half-life in circulation as compared to unmodified counterpart natriuretic compounds. Oral, parenteral, enteral, subcutaneous, pulmonary, and intravenous forms of the compounds and conjugates may be prepared as treatments and/or therapies for heart conditions particularly congestive heart failure. Modifying moieties comprising oligomeric structures having a variety of lengths and configurations are also disclosed. Analogs of the hBNP compound are also disclosed, having an amino acid sequence that is other than the native sequence.
- -
-
Page/Page column 35
(2008/12/08)
-
- DELIVERY OF BIOLOGICALLY ACTIVE MATERIALS USING CORE-SHELL TECTO (DENDRITIC POLYMERS)
-
The present invention concerns core-shell tecto (dendritic polymers) that are associated with biologically active materials (such as nucleic acids for use for RNAi and in transfection). Also included are formulations for their use. The constructs are usef
- -
-
Page/Page column 32-33
(2008/12/05)
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- The design and synthesis of highly branched and spherically symmetric fluorinated macrocyclic chelators
-
Two novel, highly fluorinated macrocyclic chelators with highly branched and spherically symmetric fluorocarbon moieties have been designed and efficiently synthesized. This is achieved by conjugating a spherically symmetric fluorocarbon moiety to the mac
- Jiang, Zhong-Xing,Yu, Y. Bruce
-
p. 215 - 220
(2008/12/20)
-
- FLUOROPOLYMER-BASED EMULSIONS FOR THE INTRAVENOUS DELIVERY OF FLUORINATED VOLATILE ANESTHETICS
-
The present invention provides therapeutic formulations, including therapeutic emulsions and nanoemulsions, and related methods for the delivery of fluorinated therapeutic compounds, including an important class of low boiling point perfluorinated and/or
- -
-
Page/Page column 33
(2008/12/06)
-
- New deuterated oligo(ethylene glycol) building blocks and their use in the preparation of surface active lipids possessing labeled hydrophilic tethers
-
(Chemical Equation Presented) For the introduction of additional analysis protocols of tethered molecules, a method is presented to prepare functionalized, deuterated oligo(ethylene glycols) from ethylene glycol-d 4. Partial oligomerization of ethylene glycol-d4 and conversion to ditosylates is accompanied by coupling reactions to prepare doubly benzyl protected oligo(ethylene glycols) with two to five repeating units. The tetramer bearing 16 deuteria was elaborated at both ends to eventually prepare 2,3-di-O-phytanyl-sn-glycerol-1-tetraethylene glycol-D,L-α-lipoic acid ester (DPTL), which bears a fully deuterated tetra(ethylene glycol) spacer group. Through linking of functionalized components, an analogue of DPTL possessing an octa(ethylene glycol) spacer group was prepared, both in deuterated and unlabeled form.
- Faragher, Robert J.,Schwan, Adrian L.
-
p. 1371 - 1378
(2008/04/12)
-
- HIGHLY FLUORINATED OILS AND SURFACTANTS AND METHODS OF MAKING AND USING SAME
-
Disclosed are compounds comprising the structure (I): In one aspect, the compounds exhibit maximum symmetric branching. Also disclosed are bilayers, micelles, coatings, and nanoparticles comprising the disclosed compounds. Also disclosed are processes for
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-
Page/Page column 44; 103; 110; 128; 130; 138
(2008/06/13)
-
- Novel amphiphilic cyclic oligosaccharides: Synthesis and self-aggregation properties
-
(Chemical Equation Presented) Novel amphiphilic cyclic disaccharide analogues, in which the saccharide units are connected through stable phosphodiester linkages (CyPLOS, Cyclic Phosphate-Linked Oligosaccharides) and decorated with long lipophilic tentacl
- Coppola, Cinzia,Saggiomo, Vittorio,Di Fabio, Giovanni,De Napoli, Lorenzo,Montesarchio, Daniela
-
p. 9679 - 9689
(2008/03/27)
-
- Ionic strength mediated hydrophobic force switching of CF 3-terminated ethylene glycol self-assembled monolayers (SAMs) on gold
-
We have synthesised novel oligo(ethylene glycol), CF3-terminated switching self-assembled monolayers, which allow the force experienced by a hydrophobic object to be controlled via the ionic strength of the environment. The Royal Society of Chemistry.
- Bonnet, Nelly,O'Hagan, David,Haehner, Georg
-
p. 5066 - 5068
(2008/09/18)
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- Synthesis of oligo(ethylene glycol) toward 44-mer
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A synthetic method for oligo(ethylene glycol) toward 44-mer (FW = 1956.35) is described. Reiteration of Williamson's ether synthesis and hydrogenation to remove protecting benzyl group affords desired oligo(ethylene glycol) toward 44-mer in moderate yields. The advantages in this method are use of commercially easily available materials as starting materials and procedures avoiding difficulty in purification of the products as much as possible.
- Ahmed, Saleh A.,Tanaka, Mutsuo
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p. 9884 - 9886
(2007/10/03)
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- Mixtures of drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same
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A non-polydispersed mixture of conjugates in which each conjugate in the mixture comprises a drug coupled to an oligomer that includes a polyalkylene glycol moiety is disclosed. The mixture may exhibit higher in vivo activity than a polydispersed mixture of similar conjugates. The mixture may be more effective at surviving an in vitro model of intestinal digestion than polydispersed mixtures of similar conjugates. The mixture may result in less inter-subject variability than polydispersed mixtures of similar conjugates.
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- Insulin polypeptide-oligomer conjugates, proinsulin polypeptide-oligomer conjugates and methods of synthesizing same
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Methods for synthesizing proinsulin polypeptides are described that include contacting a proinsulin polypeptide including an insulin polypeptide coupled to one or more peptides by peptide bond(s) capable of being cleaved to yield the insulin polypeptide with an oligomer under conditions sufficient to couple the oligomer to the insulin polypeptide portion of the proinsulin polypeptide and provide a proinsulin polypeptide-oligomer conjugate, and cleaving the one or more peptides from the proinsulin polypeptide-oligomer conjugate to provide the insulin polypeptide-oligomer conjugate. Methods of synthesizing proinsulin polypeptide-oligomer conjugates are also provided as are proinsulin polypeptide-oligomer conjugates. Methods of synthesizing C-peptide polypeptide-oligomer conjugates and other pro-polypeptide-oligomer conjugates are also provided.
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- Components for Tethered Bilayer Membranes: Synthesis of Hydrophilically Substituted Phytanol Derivatives
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In order to optimize the performance of the AMBRI biosensor (Nature 1997, 387, 580), a variety of hydrophilic linkers between the hydrophobic bilayer membrane and the gold surface have been synthesized. The principal components are prepared from phytanyl hemisuccinate, which is linked by repeating ethylene glycol or propylene glycol units to a second succinic acid unit. The syntheses of analogous substances in which the ester links are replaced by amide and by ether links are also described.
- Burns, Christopher J.,Field, Leslie D.,Morgan, Jacqueline,Petteys, Brian J.,Prashar, Jognandan,Ridley, Damon D.,Sandanayake, K.R.A. Samankumara,Vignevich, Valentina
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p. 431 - 438
(2007/10/03)
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- New facts concerning the reaction of K-, K+(15-crown-5)2 with phenyl glycidyl ether: Unexpected formation of potassium cyclopropoxide
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A new mechanism of the reaction of K-, K+(15-crown-5)2 with phenyl glycidyl ether is presented. The linear ether bond is attacked only to a small extent, if at all. As the main reaction path the oxirane bond in the β-posit
- Grobelny, Zbigniew,Stolarzewicz, Andrzej,Maercker, Adalbert,Demuth, Wolfgang
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p. 153 - 157
(2007/10/03)
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- Unexpected Cleavage of Crown Ether in the Reaction of Methyloxirane with K-,K+(15-crown-5)2
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Cleavage of oxirane and crown ether rings occurs when the supramolecular complex K-,K+(15-crown-5)2 reacts with methyloxirane in tetrahydrofuran solution. Potassium isopropoxide and potassium tetraethylene glycoxide vinyl
- Grobelny, Zbigniew,Stolarzewicz, Andrzej,Czaja, Monika,Demuth, Wolfgang,Maercker, Adalbert
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p. 8990 - 8994
(2007/10/03)
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- Ethoxylation of aralkyl alcohols
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An important reaction, the oligoaddition of ethylene oxide to the alcoholic hydroxyl group was investigated.The aralkyl alcohols were chosen as base material: benzyl-, β-phenylethyl- and γ-phenylpropyl alcohols.The first members of their homologue ethoxylated series were prepared and used as standards for the determination of the average degree of ethoxylation (IR, UV, refractive indices) and of the molar mass distribution (HPLC).
- Huszar, Klara Parlagh,Klug, Otto,Parlagh, Gyula,Rusznak, Istvan,Sallay, Peter,et al.
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p. 241 - 252
(2007/10/03)
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- A novel way for hydroxyethylation by using clay catalysts
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Hydroxyethylation of aralkyl alcohols (benzyl alcohol, 2-phenylethanol, 3-phenylpropanol) in the presence of a clay catalyst (K10) was successful. This method has some advantages in contrast with the conventional ones: effective, works at mild reaction conditions, ease the separation of catalyst from the reaction mixture.
- Sallay, Peter,Bekassy, Sandor,Ahmed, Mohamed H.,Farkas, Laszlo,Rusznak, Istvan
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p. 661 - 664
(2007/10/03)
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