108466-89-3

Usage

Uses

t-Boc-N-amido-PEG2-CH2CO2H is a heterobifunctional, PEGylated crosslinker featuring a Boc-protected amine at one end and a carboxyl group at the other. The hydrophillic PEG linker facilitates solubility in biological applications. t-Boc-N-amido-PEG2-CH2CO2H can be used for bioconjugation or as a building block for synthesis of small molecules, conjugates of small molecules and/or biomolecules, or other tool compounds for chemical biology and medicinal chemistry that require ligation. Examples of applications include its synthetic incorporation into antibody-drug conjugates or proteolysis-targeting chimeras (PROTAC? molecules) for targeted protein degradation.

Upstream product

• 79-08-3 bromoacetic acid 
• 139115-91-6 2-(2-tert-butyloxycarbonylaminoethoxy)ethanol 
• 305-53-3 monosodium iodoacetate 
• 24424-99-5 di-tert-butyl dicarbonate 
• 134978-97-5 [2-(N-2-amino ethoxy)ethoxy] acetic acid 
• 560088-79-1 dicyclohexylammonium 1-(tert-butyloxycarbonylamino)-3,6-dioxa-octanoate 
• 134979-01-4 2-(2-(2-amino-ethoxy)ethoxy)acetic acid hydrochloride 
• 1254054-91-5 C₁₈H₂₇NO₆ 
• 105-36-2 ethyl bromoacetate 
• 929-06-6 2-(2-Aminoethoxy)ethanol 
• 166108-71-0 8-(9-fluorenylmethyloxycarbonyl-amino)-3,6-dioxaoctanoic acid 
• 64887-49-6 α-cyclodextrin-Methyl Orange complex 
• 141484-63-1 C₃₇H₄₇N₃⁽²⁺⁾*C₃₆H₆₀O₃₀*2Br^(1-) 

Downstream Products

• 1154625-12-3 C₃₄H₄₇ClN₆O₈ 
• 1229593-79-6 rhodamine-(AEEA)-Pro-Lys-Lys-Lys-Arg-Lys-Val-Gly-NH₂; AEEA = 2-aminoethoxyethoxyacetyl spacer 
• 1246261-24-4 C₄₇H₆₄N₄O₁₅ 
• 1254054-91-5 C₁₈H₂₇NO₆ 
• 1310327-56-0 1-((R)-9-amino-4-(2,2-diphenylacetamido)-1-(4-hydroxyphenyl)-3,11-dioxo-13,16-dioxa-2,8,10-triazaoctadec-9-en-18-yl)-4-((E)-2-(1,2,3,5,6,7-hexahydropyrido[3,2,1-ij]quinolin-9-yl)ethenyl)-2,6-dimethylpyridinium hydrotrifluoroacetate trifluoroacetate 
• 1310327-62-8 1-((R)-9-amino-4-(2,2-diphenylacetamido)-1-(4-hydroxyphenyl)-3,11-dioxo-13,16-dioxa-2,8,10-triazaoctadec-9-en-18-yl)-4-((1E,3E)-4-(4-(dimethylamino)phenyl)buta-1,3-dienyl)-2,6-dimethylpyridinium hydrotrifluoroacetate trifluoroacetate 
• 1365253-82-2 tert-butyl(2,2-dimethyl-11-oxo-3,3-diphenyl-4,7,13,16-tetraoxa-10-aza-3-silaoctadecan-18-yl)carbamate 
• 1365253-84-4 benzyl 3-(3-(((2,2-dimethyl-4,13-dioxo-3,8,11,17-tetraoxa-5,14-diazanonadecan-19-yl)oxy)sulfonyl)benzamido)propanoate 
• 1432471-16-3 (2S)-N^ω-(8-amino-3,6-dioxaoctanoyl)-N-[2-(3,5-dioxo-1,2-diphenyl-1,2,4-triazolidin-4-yl)-ethyl]-N^α-[2-(1-{2-oxo-2-[4-(6-oxo-6,11-dihydro-5H-dibenzo[b,e]azepin-11-yl)piperazin-1-yl]ethyl}cyclopentyl)acetyl]argininamide 
• 1432471-25-4 (2S)-N-[2-(3,5-dioxo-1,2-diphenyl-1,2,4-triazolidin-4-yl)ethyl]-N^α-[2-(1-{2-oxo-2-[4-(6-oxo-6,11-dihydro-5H-dibenzo[b,e]azepin-11-yl)piperazin-1-yl]ethyl}cyclopentyl)acetyl]-N^ω-(8-propanoylamino-3,6-dioxaoctanoyl)argininamide 
• 134978-97-5 [2-(N-2-amino ethoxy)ethoxy] acetic acid 

Relevant academic research and scientific papers

Synthesis, Biological Evaluation of Fluorescent 23-Hydroxybetulinic Acid Probes, and Their Cellular Localization Studies

23-Hydroxybetulinic acid (23-HBA) is a complex lupane triterpenoid, which has attracted increasing attention as an anticancer agent. However, its detailed mechanism of anticancer action remains elusive so far. To reveal its anticancer mode of action, a series of fluorescent 23-HBA derivatives conjugated with coumarin dyes were designed, synthesized, and evaluated for their antiproliferative activities. Subcellular localization and uptake profile studies of representative fluorescent 23-HBA probe 26c were performed in B16F10 cells, and the results suggested that probe 26c was rapidly taken up into B10F10 cells in a dose-dependent manner and mitochondrion was the main site of its accumulation. Further mode of action studies implied that the mitochondrial pathway was involved in 23-HBA-mediated apoptosis. Together, our results provided new clues for revealing the molecular mechanism of natural product 23-HBA for its further development into an antitumor agent.

Controlling cellular distribution of drugs with permeability modifying moieties

Phenotypic screening provides compounds with very limited target cellular localization data. In order to select the most appropriate target identification methods, determining if a compound acts at the cell-surface or intracellularly can be very valuable. In addition, controlling cell-permeability of targeted therapeutics such as antibody-drug conjugates (ADCs) and targeted nanoparticle formulations can reduce toxicity from extracellular release of drug in undesired tissues or direct activity in bystander cells. By incorporating highly polar, anionic moieties via short polyethylene glycol linkers into compounds with known intracellular, and cell-surface targets, we have been able to correlate the cellular activity of compounds with their subcellular site of action. For compounds with nuclear (Brd, PARP) or cytosolic (dasatinib, NAMPT) targets, addition of the permeability modifying group (small sulfonic acid, polycarboxylic acid, or a polysulfonated fluorescent dye) results in near complete loss of biological activity in cell-based assays. For cell-surface targets (H3, 5HT1A, β2AR) significant activity was maintained for all conjugates, but the results were more nuanced in that the modifiers impacted binding/activity of the resulting conjugates. Taken together, these results demonstrate that small anionic compounds can be used to control cell-permeability independent of on-target activity and should find utility in guiding target deconvolution studies and controlling drug distribution of targeted therapeutics.

Cell-Surface Receptor-Ligand Interaction Analysis with Homogeneous Time-Resolved FRET and Metabolic Glycan Engineering: Application to Transmembrane and GPI-Anchored Receptors

Ligand-binding assays are the linchpin of drug discovery and medicinal chemistry. Cell-surface receptors and their ligands have traditionally been characterized by radioligand-binding assays, which have low temporal and spatial resolution and entail safety risks. Here, we report a powerful alternative (GlycoFRET), where terbium-labeled fluorescent reporters are irreversibly attached to receptors by metabolic glycan engineering. For the first time, we show time-resolved fluorescence resonance energy transfer between receptor glycans and fluorescently labeled ligands. We describe GlycoFRET for a GPI-anchored receptor, a G-protein-coupled receptor, and a heterodimeric cytokine receptor in living cells with excellent sensitivity and high signal-to-background ratios. In contrast to previously described methods, GlycoFRET does not require genetic engineering or antibodies to label receptors. Given that all cell-surface receptors are glycosylated, we expect that GlycoFRET can be generalized with applications in chemical biology and biotechnology, such as target engagement, receptor pharmacology, and high-throughput screening.

HaloTag protein-mediated site-specific conjugation of bioluminescent proteins to quantum dots

On the dot: A genetically engineered haloalkane dehalogenase was used to conjugate Renilla luciferase to quantum dots (see picture). The quantum dots can emit light through bioluminescence resonance energy transfer (BRET). This specific conjugation occurs upon simple mixing under mild conditions, and may be applied for specific in vivo labeling of proteins with quantum dots for imaging. (Figure Presented).

Polyethylene glycol coupling medicine as well as preparation method and application thereof

The invention relates to the technical field of medicines, relates to a polyethylene glycol coupled drug as well as a preparation method and an application thereof, and in particular relates to a polyethylene glycol coupled drug as shown in a formula I or pharmaceutically acceptable salt thereof. The invention also relates to a preparation method of the polyethylene glycol coupled drug or the pharmaceutically acceptable salt thereof, a pharmaceutical composition containing the polyethylene glycol coupled drug or the pharmaceutically acceptable salt thereof, and the application of the polyethylene glycol coupled drug or the pharmaceutically acceptable salt thereof in preparation of drugs.

DEGRADATION OF BRUTON'S TYROSINE KINASE (BTK) BY CONJUGATION OF BTK INIDBITORS WITH E3 LIGASE LIGAND AND METHODS OF USE

Disclosed herein are novel bifunctional compounds formed by conjugating BTK inhibitor moieties with E3 ligase Ligand moieties, which function to recruit targeted proteins to E3 ubiquitin ligase for degradation, and methods of preparation and uses thereof.

Design, Synthesis, and Evaluation of VHL-Based EZH2 Degraders to Enhance Therapeutic Activity against Lymphoma

Traditional EZH2 inhibitors are developed to suppress the enzymatic methylation activity, and they may have therapeutic limitations due to the nonenzymatic functions of EZH2 in cancer development. Here, we report proteolysis-target chimera (PROTAC)-based EZH2 degraders to target the whole EZH2 in lymphoma. Two series of EZH2 degraders were designed and synthesized to hijack E3 ligase systems containing either von Hippel-Lindau (VHL) or cereblon (CRBN), and some VHL-based compounds were able to mediate EZH2 degradation. Two best degraders, YM181 and YM281, induced robust cell viability inhibition in diffuse large B-cell lymphoma (DLBCL) and other subtypes of lymphomas, outperforming a clinically used EZH2 inhibitor EPZ6438 (tazemetostat) that was only effective against DLBCL. The EZH2 degraders displayed promising antitumor activities in lymphoma xenografts and patient-derived primary lymphoma cells. Our study demonstrates that EZH2 degraders have better therapeutic activity than EZH2 inhibitors, which may provide a potential anticancer strategy to treat lymphoma.

Method for preparing semaglutide side chain by liquid phase method

The invention discloses a method for preparing a semaglutide side chain. The preparation method comprises the following steps: protecting amino of an initial raw material 2-(2-aminoethoxy) ethanol byusing R1; then carrying out nucleophilic substitution reaction with alpha halogenated ester to prolong a carbon chain; preparing an aliphatic chain with two protected ends by a one-pot method; removing a protecting group at one end of each aliphatic chain and condensing to obtain a compound 7; removing the R1 protecting group to obtain a compound 8, performing condensation reaction on the compound8 and fluorenylmethoxycarbonyl-L-glutamic acid 1-tert-butyl ester to obtain a compound 10, removing the fluorenylmethoxycarbonyl, performing amidation condensation reaction on the compound 10 and 18-(tert-butoxy)-18-oxooctadecanoic acid to obtain a compound 13, and removing the R2 protecting group to obtain a target product chain 1. Compared with solid-phase synthesis, the method disclosed by theinvention is lower in cost and wider in selection of protecting groups, and has industrial production and application prospects.

Method for synthesizing semaglutide side chain in liquid-phase convergent manner

The invention discloses a method for synthesizing a semaglutide side chain 1 in a liquid-phase convergent manner. The method comprises the steps: protecting amino of a raw material 2-(2-aminoethoxy)ethanol by using R1; then carrying out nucleophilic substitution reaction with ethyl bromoacetate; carrying out ester hydrolysis in one pot to obtain a compound 4; protecting carboxyl of the compound 4with R2; removing R1 to obtain a compound 6; carrying out condensation reaction on the compound 6 and fluorenylmethoxycarbonyl-L-glutamic acid 1-tert-butyl ester, to obtain a compound 8; removing R2 of the compound 8, and carrying out a coupling reaction with the compound 6 to obtain a compound 10; removing Fmoc of the compound 10, carrying out an amidation condensation coupling reaction with 18-(tert-butoxy)-18-oxooctadecanoic acid to obtain a compound 13; and removing R2 of the compound 13 to obtain the product 1. The method has the advantages of effective and controllable synthesis process,low cost and high yield, and can be suitable for large-scale production.

Convergent liquid-phase synthesis method of semaglutide side chain

A synthesis method of a semaglutide side chain 1 comprises the following steps: protecting a terminal amino group of a raw material diglycolamine 2 by using R1, then carrying out nucleophilic substitution reaction with alpha halogenated ester, and carrying out ester hydrolysis in one pot to obtain a compound 4; protecting the free carboxyl of the compound 4 by R2, and removing the R1 protected group to obtain a compound 6; carrying out condensation reaction on a compound 7 and the compound 6 to obtain a compound 8; removing fluorenylmethoxycarbonyl of the compound 8, carrying out an amidationcondensation coupling reaction on the compound 8 and 18-(tert-butoxy)-18-oxooctadecanoic acid to obtain a compound 11; removing the R2 protected group of the compound 11, carrying out a condensation coupling reaction on the compound 11 and the compound 6 to obtain a compound 13; and removing the R2 protected group of the compound 13 to obtain the chain 1. A convergent synthesis method is used to reduce the reaction cost and shorten the reaction time, the synthesis process is effective and controllable, the cost is low, the yield is high, and the method is suitable for large-scale production.