3973-18-0Relevant articles and documents
Fluorogenic tagging of peptides via Cys residues using thiol-specific vinyl sulfone affinity tags
Cserép, Gergely B.,Baranyai, Zsuzsa,Komáromy, Dávid,Horváti, Kata,Bosze, Szilvia,Kele, Péter
, p. 5961 - 5965 (2014)
Fluorescent tagging of Cys-containing peptides is presented herein. The procedure follows a two-step sequential reaction scheme using thiol specific bifunctional chemical reporters and fluorogenic labels. Vinyl-sulfone bearing chemical reporters have been synthesized and demonstrated to selectively modify cysteine under physiological conditions in the presence of other nucleophilic amino acids. Bifunctional chemical reporters decorated with a terminal alkyne moiety, suitable for modification with azide containing fluorogenic labels were also synthesized. Such fluorogenic (turn on) labels in combination with these new vinyl-sulfone tags can be used generally in fluorescent modulation schemes of thiol-bearing biomolecules.
Observation of Circularly Polarized Luminescence of the Excimer from Two Perylene Cores in the Form of [4]Rotaxane
Hayashi, Koichiro,Miyaoka, Yuta,Ohishi, Yuki,Uchida, Taka-aki,Iwamura, Munetaka,Nozaki, Koichi,Inouye, Masahiko
, p. 14613 - 14616 (2018)
A perylene-based [4]rotaxane was synthesized by the Sonogashira coupling of the 2:2 inclusion complex consisting of two alkynylperylenes and two γ-cyclodextrins with terphenyl-type stopper molecules. The [4]rotaxane showed orange emission attributable to the spatially restricted alkynylperylene excimer with a high fluorescence quantum yield of Φf=0.15. The excimer emission was circularly polarized as a result of the asymmetrically twisted perylene pair under the influence of chirality of γ-cyclodextrin. The glum value of the excimer emission was determined to be ?2.1×10?2 at 573 nm, as large as those of the corresponding known pyrene-based series. This is the first example, in which circularly polarized luminescence was clearly observed from the excimer of a pair of perylene cores.
TAU-PROTEIN TARGETING COMPOUNDS AND ASSOCIATED METHODS OF USE
-
Paragraph 0566; 0567; 1278; 1279, (2021/02/12)
The present disclosure relates to bifunctional compounds, which find utility as modulators of tan 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 tan protein, such that tan protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of tan. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of tan protein. Diseases or disorders that result from aggregation or accumulation of tan protein are treated or prevented with compounds and compositions of the present disclosure.
BRANCHED MOIETY FOR USE IN CONJUGATES
-
Page/Page column 38, (2021/04/30)
A tri-functional linker moiety: formula (I), where X and Y are linking chains, and its use for preparing dual-mechanistic drug conjugates, preferably in a site-specific manner.
Discovery and mechanism of action studies of 4,6-diphenylpyrimidine-2-carbohydrazides as utrophin modulators for the treatment of Duchenne muscular dystrophy
Vuorinen, Aini,Wilkinson, Isabel V.L.,Chatzopoulou, Maria,Edwards, Ben,Squire, Sarah E.,Fairclough, Rebecca J.,Bazan, Noelia Araujo,Milner, Josh A.,Conole, Daniel,Donald, James R.,Shah, Nandini,Willis, Nicky J.,Martínez, R. Fernando,Wilson, Francis X.,Wynne, Graham M.,Davies, Stephen G.,Davies, Kay E.,Russell, Angela J.
supporting information, (2021/05/03)
Duchenne muscular dystrophy is a fatal disease with no cure, caused by lack of the cytoskeletal protein dystrophin. Upregulation of utrophin, a dystrophin paralogue, offers a potential therapy independent of mutation type. The failure of first-in-class utrophin modulator ezutromid/SMT C1100 in Phase II clinical trials necessitates development of compounds with better efficacy, physicochemical and ADME properties and/or complementary mechanisms. We have discovered and performed a preliminary optimisation of a novel class of utrophin modulators using an improved phenotypic screen, where reporter expression is derived from the full genomic context of the utrophin promoter. We further demonstrate through target deconvolution studies, including expression analysis and chemical proteomics, that this compound series operates via a novel mechanism of action, distinct from that of ezutromid.
Novel camptothecin derivative, and preparation method and application thereof
-
Paragraph 0087-0088; 0095-0096, (2020/03/12)
The invention relates to a novel camptothecin derivative and application thereof, a tumor cell growth inhibitor, a ternary complex, and a method for improving the solubility of the camptothecin derivative. The camptothecin derivative is formed by modifying a substance represented by formula I through glycosylated triazole in the position R3. In a structural formula represented by the formula I, R1represents H, alkyl of C1-10, deuterated alkyl of the C1-10, or halogenated alkyl of the C1-10; R2 represents H, CH2N(CH3)2 or CH2N(CD3)2; R4 represents H, and X represents N, O or S; L represents polypeptide, C1-20 linear alkyl or a derivative thereof, a C1-20 linear or branched acyl derivative, or C2-100 ethylene glycol or a derivative thereof. The camptothecin derivative has high solubility, prepared anticancer drugs have the advantages of wide anticancer spectrum and high safety, and the in-vivo anticancer activity is superior to that of irinotecan hydrochloride.
Flavone derivative for treating tumor and application thereof
-
Paragraph 0121-0123, (2020/09/16)
The invention provides a flavone derivative represented by a formula I and pharmaceutically acceptable salt, hydrate or solvate thereof. In the formula I, R1 H, is 1-4 alkyl, amino or C1-4 acyl; R2 isisopentenyl or 2-hydroxy isopentyl; R3 is H, methyl or deuterated methyl; R4 represents C1-4 alkyl, amino or C1-4 acyl or R5 represents monosaccharide residue or oligosaccharide residue; and L represents polypeptide, C1-C20 straight chain alkyl or derivative thereof, C1-C20 straight chain or branched chain acyl derivative, C1-C20 ethylene glycol or derivative thereof, wherein Y is an integer of 0to 100, b is an integer of 1 to 100, C is an integer of 1 to 10, d is an integer of 0 to 100, and e is an integer of 0 to 100. The flavone derivative has high-efficiency broad-spectrum anticancer activity.
CGRP ANTAGONIST COMPOUNDS
-
Page/Page column 85, (2020/12/30)
The disclosures herein relate to novel compounds of Formula (1a): and salts thereof, wherein W, Z, L, R1and R2 are defined herein, and their use in treating, preventing, ameliorating, controlling or reducing the risk of disorders associated with CGRP receptors.
TAU-PROTEIN TARGETING PROTACS AND ASSOCIATED METHODS OF USE
-
Paragraph 0858; 0859, (2018/05/24)
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.
Synthetic antibody protein mimics of infliximab by molecular scaffolding on novel CycloTriVeratrilene (CTV) derivatives
Longin, Ond?ej,Hezwani, Mohammed,Van De Langemheen, Helmus,Liskamp, Rob M. J.
, p. 5254 - 5274 (2018/08/04)
Syntheses of novel semi-orthogonally protected CycloTriVeratrilene (CTV) analogues with enhanced water solubility, that is 3 and 4, derived from the previously described CTV scaffold derivative 2 are described here. These scaffolds 2-4 enabled a sequential introduction of three different complementarity determining region (CDR) mimics via Cu(i)-catalysed azide-alkyne cycloaddition towards medium-sized protein mimics denoted as "synthetic antibodies". The highly optimised sequential introduction enabled selective attachment of three different CDR mimics in a one-pot fashion. This approach of obtaining synthetic antibodies, demonstrated by the synthesis of paratope mimics of monoclonal antibody infliximab (Remicade), provided a facile access to a range of (highly) pre-organised molecules bearing three different (cyclic) peptide segments and may find a wide range of applications in the field of protein-protein interaction disruptors as well as in the development of synthetic vaccines or lectin mimics. The prepared synthetic antibodies were tested for their affinity towards tumour necrosis factor alpha using surface plasmon resonance and synthetic antibodies with micromolar affinities were uncovered.
