1493802-77-9

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General Description

The chemical compound, ((1R,8S,9s)-bicyclo[6.1.0]non-4-yn-9-yl)methyl (2,5-dioxopyrrolidin-1-yl) carbonate, is a bicyclic non-steroidal compound that contains a carbonate group and a pyrrolidin-1-yl group. It has a molecular structure that includes a bicyclo[6.1.0]non-4-yn-9-yl moiety attached to a carbonate and pyrrolidin-1-yl groups, which are important for its functionality and reactivity. ((1R,8S,9s)-bicyclo[6.1.0]non-4-yn-9-yl)methyl (2,5-dioxopyrrolidin-1-yl) carbonate may have applications in organic synthesis, pharmaceuticals, and materials science, and further research into its properties and potential uses is ongoing.

Upstream product

• 1552-12-1 1,5-cis,cis-cyclooctadiene 
• 74124-79-1 di(succinimido) carbonate 
• 1263166-90-0 (1R,8S,9S)‐bicyclo[6.1.0]non‐4‐yn‐9‐ylmethanol 
• 1263291-41-3 (1α,8α,9α)-bicyclo[6.1.0]non-4-yn-9-ylmethanol 

Downstream Products

• 1426827-84-0 (RS)-endo-bicyclo[6.1.0]non-4-yn-9-ylmethyl (8-dimethoxytrityloxy-6-hydroxy-4,8-dioxaoctyl)carbamate 

Relevant academic research and scientific papers

Multivalent zanamivir-bovine serum albumin conjugate as a potent influenza neuraminidase inhibitor

A multivalent Zanamivir (ZA) conjugate as new anti-influenza agent was prepared. Specifically, multiple copies of ZA with a C7 azido-terminated linker were covalently attached onto alkynemodified bovine serum albumin (BSA) via copper-free click reaction. The loading number of ZA was determined by MALDI-TOF. Primary neuraminidase (NA) inhibition assay showed that this conjugate retained some NA inhibitory activity compared to its parent ZA monomer. Moreover, the ZA-BSA conjugate was not cytotoxic with concentrations up to 1 μM.

A Bioorthogonal-Activated Fluorescence Turn-On Probe Based on Nitrone-Modified 1,8-Naphthalimide for Live-Cell Imaging

A nitrone-modified 1,8-naphthalimide was designed as a novel bioorthogonal-activated turn-on probe based on strain-promoted alkyne-nitrone cycloaddition (SPANC). The bioorthogonal cycloadducts were subsequently transformed into fluorescent rearrangement products by photo-acceleration, which exhibited significant fluorescence enhancement, large stokes shift, and high fluorescence quantum yield. DFT calculations were performed to elucidate the fluorescence OFF-ON mechanism. This fluorogenic strategy was successfully applied to labeling of proteins and visualizing mitochondria in live cells in real time.

VIA CYCLOADDITION BILATERALLY FUNCTIONALIZED ANTIBODIES

The present invention provides antibody-payload conjugates having a payload-to-antibody ratio of 1. The antibody-payload conjugate having structure (1): Formula (1) wherein: - a, b and c are each independently 0 or 1; - L1, L2 and L3 are linkers; - D is a payload; - BM is a branching moiety; - Z are connecting groups obtainable by a cycloaddition reaction. The invention further provides a method for preparing the antibody-payload conjugate according to the invention, an intermediate compound in that preparation method, and medical uses of the antibody-payload conjugate according to the invention.

CONJUGATES OF ANTIBODIES AN IMMUNE CELL ENGAGERS

The present invention concerns a process for preparing a multispecific antibody construct, comprising conjugating a functionalized antibody Ab(F)x containing x reactive moieties F, wherein x is an integer in the range 1 – 10, and an immune cell

VIA CYCLOADDITION BILATERALLY FUNCTIONALIZED ANTIBODIES

The present invention provides antibody-payload conjugates having a payload-to-antibody ratio of 1. The antibody-payload conjugate is according to structure (1): formula (1), wherein: - a, b, c and d are each independently 0 or 1; - e is an integer in the

Chemical Targeting of Voltage Sensitive Dyes to Specific Cells and Molecules in the Brain

Voltage sensitive fluorescent dyes (VSDs) are important tools for probing signal transduction in neurons and other excitable cells. The impact of these highly lipophilic sensors has, however, been limited due to the lack of cell-specific targeting methods in brain tissue or living animals. We address this key challenge by introducing a nongenetic molecular platform for cell- and molecule-specific targeting of synthetic VSDs in the brain. We employ a dextran polymer particle to overcome the inherent lipophilicity of VSDs by dynamic encapsulation and high-affinity ligands to target the construct to specific neuronal cells utilizing only native components of the neurotransmission machinery at physiological expression levels. Dichloropane, a monoamine transporter ligand, enables targeting of dense dopaminergic axons in the mouse striatum and sparse noradrenergic axons in the mouse cortex in acute brain slices. PFQX in conjunction with ligand-directed acyl imidazole chemistry enables covalent labeling of AMPA-type glutamate receptors in the same brain regions. Probe variants bearing either a classical electrochromic ANEP dye or state-of-the-art VoltageFluor-type dye respond to membrane potential changes in a similar manner to the parent dyes, as shown by whole-cell patch recording. We demonstrate the feasibility of optical voltage recording with our probes in brain tissue with one-photon and two-photon fluorescence microscopy and define the signal limits of optical voltage imaging with synthetic sensors under a low photon budget determined by the native expression levels of the target proteins. This work demonstrates the feasibility of a chemical targeting approach and expands the possibilities of cell-specific imaging and pharmacology.

MOLECULAR LOGIC GATES FOR CONTROLLED MATERIAL DEGRADATION

The present disclosure features, inter alia, a cyclic multifunctional linker, including at least two cleavable moieties; at least two connecting chains connected to the at least two cleavable moieties to provide a cyclic structure; and at least two linkin

FUSOGENIC LIPOSOMES, COMPOSITIONS, KITS AND USE THEREOF FOR TREATING CANCER

A fusogenic liposome comprising a lipid bilayer comprising a plurality of lipid molecules having 14 to 24 carbon atoms, wherein at least one of said lipid molecules is functionalised with a first functional group of a specific binding pair capable of binding to a complementary second functional group of said binding pair; and optionally further comprising an immune system activating agent functionalised with a complementary second functional group of said binding pair bound to said first functional group is provided. Methods of treatment of cancer using the fusogenic liposome are also provided.

Beyond azide-alkyne click reaction: Easy access to 18F-labelled compounds via nitrile oxide cycloadditions

Radiofluorinated 4-fluorobenzonitrile oxide and N-hydroxy-4- fluorobenzimidoyl chloride rapidly react with different alkenes and alkynes under mild conditions. These cycloadditions are suitable for the preparation of low-molecular weight radiopharmaceutic

Genetic encoding of bicyclononynes and trans-cyclooctenes for site-specific protein labeling in vitro and in live mammalian cells via rapid fluorogenic diels-alder reactions

Rapid, site-specific labeling of proteins with diverse probes remains an outstanding challenge for chemical biologists. Enzyme-mediated labeling approaches may be rapid but use protein or peptide fusions that introduce perturbations into the protein under study and may limit the sites that can be labeled, while many "bioorthogonal" reactions for which a component can be genetically encoded are too slow to effect quantitative site-specific labeling of proteins on a time scale that is useful for studying many biological processes. We report a fluorogenic reaction between bicyclo[6.1.0]non-4-yn-9- ylmethanol (BCN) and tetrazines that is 3-7 orders of magnitude faster than many bioorthogonal reactions. Unlike the reactions of strained alkenes, including trans-cyclooctenes and norbornenes, with tetrazines, the BCN-tetrazine reaction gives a single product of defined stereochemistry. We have discovered aminoacyl-tRNA synthetase/tRNA pairs for the efficient site-specific incorporation of a BCN-containing amino acid, 1, and a trans-cyclooctene- containing amino acid 2 (which also reacts extremely rapidly with tetrazines) into proteins expressed in Escherichia coli and mammalian cells. We demonstrate the rapid fluorogenic labeling of proteins containing 1 and 2 in vitro, in E. coli, and in live mammalian cells. These approaches may be extended to site-specific protein labeling in animals, and we anticipate that they will have a broad impact on labeling and imaging studies.