356046-26-9Relevant articles and documents
Transferrin-Appended Nanocaplet for Transcellular siRNA Delivery into Deep Tissues
Kohata, Ai,Hashim,Okuro, Kou,Aida, Takuzo
, p. 2862 - 2866 (2019)
Transferrin (Tf) is known to induce transcytosis, which is a consecutive endocytosis/exocytosis event. We developed a Tf-appended nanocaplet (TfNC?siRNA) for the purpose of realizing siRNA delivery into deep tissues and RNA interference (RNAi)
Catalytic Synthesis of PEGylated EGCG Conjugates that Disaggregate Alzheimer's Tau
El Khoury, Anton,Seidler, Paul M.,Eisenberg, David S.,Harran, Patrick G.
, p. 4263 - 4271 (2021/06/18)
The naturally occurring flavonoid ( )-epigallocatechin gallate (EGCG) is a potent disaggregant of tau fibrils. Guided by the recent cryo-electron microscopy (cryoEM) structure of EGCG bound to fibrils of tau derived from an Alzheimer s brain donor, methods to site-specifically modify the EGCG D-ring with aminoPEGylated linkers are reported. The resultant molecules inhibit tau fibril seeding by Alzheimer s brain extracts. Formulations of aminoPEGylated EGCG conjugated to the (quasi)-brain-penetrant nanoparticle Ferumoxytol inhibit seeding by AD-tau with linker length affecting activity. The protecting groupfree catalytic cycloaddition of amino azides to mono-propargylated EGCG described here provides a blueprint for access to stable nanoparticulate forms of EGCG potentially useful as therapeutics to eliminate Alzheimer s-related tau tangles.
Design and Synthesis of Oleanolic Acid Trimers to Enhance Inhibition of Influenza Virus Entry
Huang, Boxuan,Li, Weijia,Mu, Yu,Shao, Liang,Su, Yangqing,Sun, Mengsi,Xu, Huan,Yang, Fan,Yu, Fei,Zhang, Jihong,Zhang, Yuan
, p. 1759 - 1765 (2021/11/18)
Influenza is a major threat to millions of people worldwide. Entry inhibitors are of particular interest for the development of novel therapeutic strategies for influenza. We have previously discovered oleanolic acid (OA) to be a mild influenza hemagglutinin (HA) inhibitor. In this work, inspired by the 3D structure of HA as a homotrimeric receptor, we designed and synthesized 15 OA trimers with different linkers and central region via the copper-catalyzed azide-alkyne cycloaddition reaction. All of the OA trimers were evaluated for their antiviral activities in vitro, and 12c, 12e, 13c, and 13d were observed to exhibit robust potency (IC50 in the submicromolar range) against influenza A/WSN/33 (H1N1) virus that was stronger than that observed with oseltamivir. In addition, these compounds also displayed strong biological activity against A/Hong Kong/4801/2014 and B/Sichuan/531/2018 (BV). The results of hemagglutination inhibition assays and surface plasmon resonance binding assays suggest that these OA trimers may interrupt the interaction between the HA protein of influenza virus and the host cell sialic acid receptor, thus blocking viral entry. These findings highlight the utility of multivalent OA conjugates to enhance the ligand-target interactions in anti-influenza virus drug design and are also helpful for studying antiviral drugs derived from natural products.
COMPOSITIONS AND METHODS RELATED TO MOLECULAR CONJUGATION
-
Page/Page column 46; 47, (2021/06/11)
The invention relates to activated Michael acceptor (AMA) compounds that can undergo conjugation with biomolecules containing Michael donor moieties, thereby providing plasma-stable antibody-drug conjugates (ADCs). Pharmaceutical compositions of the ADCs are disclosed as well. Also provided herein are a number of applications (e.g., therapeutic applications) in which the compositions are useful.
Synthesis of peptide homo- and heterodimers as potential mimics of platelet-derived growth factor BB
Stubbing, Louise A.,Kaur, Harveen,Feng, Sheryl X.,Aalderink, Miranda,Dragunow, Michael,Brimble, Margaret A.
, (2020/07/28)
Pericyte loss is correlated with blood-brain barrier leakage in neurological disorders such as Alzheimer's disease. The platelet-derived growth factor receptor β (PDGFRβ)/platelet-derived growth factor BB (PDGF-BB) signalling pathway is key to the regulation of pericyte survival and proliferation. A series of peptide dimers mimicking the ligand PDGF-BB were prepared in the hope of stimulating PDGFRβ internalisation and activation of this pathway. Copper-catalysed azide-alkyne cycloaddition of peptide monomers with PEGylated linkers of varying length afforded the desired peptide dimers. Evaluation of the peptide dimers in human brain pericyte assays revealed no effect on PDGFRβ internalisation nor cell proliferation at concentrations 10 μM. The peptide dimers also did not act as antagonists at PDGFRβ at concentrations 10 μM.
Sialyloligosaccharide-quantum dot conjugate as well as preparation method and application thereof
-
, (2020/03/17)
The invention relates to a sialyloligosaccharide-quantum dot conjugate, a preparation method of the conjugate, and an application of the conjugate in virus detection. The sialyloligosaccharide-quantumdot conjugate provided by the invention is prepared by
MONOMER AND MULTIMERIC ANTI-HBV AGENTS
-
, (2020/05/15)
The present invention is directed to compounds, compositions and methods for preventing, treating or curing hepatitis B (HBV) infection in human subjects or other animal hosts. The compounds are as also pharmaceutically acceptable, salts, prodrugs, and other derivatives thereof as pharmaceutical compositions and methods for treatment, prevention or eradication of HBV infection.
Bivalent HIV-1 fusion inhibitors based on peptidomimetics
Kobayakawa, Takuya,Ebihara, Kento,Tsuji, Kohei,Kawada, Takuma,Fujino, Masayuki,Honda, Yuzuna,Ohashi, Nami,Murakami, Tsutomu,Tamamura, Hirokazu
, (2020/11/07)
Membrane fusion is a valid target for inhibition of HIV-1 replication. A 34-mer fragment peptide (C34), which is contained in the HIV-1 envelope protein gp41, has significant anti-HIV activity. Previously, a dimeric derivative of C34 linked by a disulfide bridge at its C-terminus was found to have more potent anti-HIV activity than the C34 peptide monomer. To date, several peptidomimetic small inhibitors have been reported, but most have lower potency than peptide derivatives related to C34. In the present study we applied this dimerization concept to these peptidomimetic small inhibitors and designed several bivalent peptidomimetic HIV-1 fusion inhibitors. The importance of the length of linkers crosslinking two peptidomimetic compounds was demonstrated and several potent bivalent inhibitors containing tethered peptidomimetics were produced.
EXENATIDE MODIFIER AND USE THEREOF
-
, (2018/05/24)
Disclosed are an exenatide modifier for connecting the exenatide to a fatty chain with a carboxy in the terminus thereof by means of a hydrophilic connecting arm, and a use thereof in preparing drugs serving as a GLP-1 receptor agonist; a use in preparing drugs for preventing and/or treating diseases and/or symptoms associated with a low GLP-1 receptor activity; a use in preparing drugs for diseases and/or symptoms associated with glycometabolism; a use in preparing drugs for diabetes; a use in preparing drugs for fatty liver disease, and a use in preparing drugs for losing weight.
Cross-linked cyclic porphyrin derivative and method for preparing the same
-
Paragraph 0158-0163, (2018/07/07)
The present invention relates to a cross-linked cyclic porphyrin derivative and to a manufacturing method thereof. By using the crosslinked cyclic porphyrin derivative, it is possible to measure a change in color selectively when cations and anions are present together, and thus the cations and the anions, preferably Li cations and halogen anions, can be selectively detected without any separate labels.COPYRIGHT KIPO 2018