Name: (E)-Cyclooct-4-en-1-yl (2,5-dioxopyrrolidin-1-yl) carbonate
Brand: BOC Sciences
Rating: 5 (1 reviews)

Synonyms

TCO-NHS ester; TCO-NHS; (E)-Cyclooct-4-en-1-yl (2,5-dioxopyrrolidin-1-yl) carbonate

IUPAC Name

[(4E)-cyclooct-4-en-1-yl] (2,5-dioxopyrrolidin-1-yl) carbonate

Canonical SMILES

C1CC=CCCC(C1)OC(=O)ON2C(=O)CCC2=O

InChI

InChI=1S/C13H17NO5/c15-11-8-9-12(16)14(11)19-13(17)18-10-6-4-2-1-3-5-7-10/h1-2,10H,3-9H2/b2-1+

InChIKey

OUGQJOKGFAIFAQ-OWOJBTEDSA-N

Solubility

Soluble

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Pictograms

Harmful

Signal Word

Warning

(E)-Cyclooct-4-en-1-yl (2,5-dioxopyrrolidin-1-yl) carbonate, a versatile organic compound widely utilized in organic synthesis and material science, has diverse applications across various fields. Here are four key applications presented with high perplexity and burstiness:

Polymer Chemistry: Acting as a foundational element in polymer synthesis, (E)-Cyclooct-4-en-1-yl (2,5-dioxopyrrolidin-1-yl) carbonate enables the creation of polymers endowed with exceptional characteristics like enhanced thermal stability and mechanical robustness. These polymers, vital in coatings, adhesives, and high-performance materials, owe their unique properties to the intricate chemical structure of the compound, fostering a myriad of industrial applications.

Drug Delivery Systems: Pushing the boundaries of drug delivery technology, (E)-Cyclooct-4-en-1-yl (2,5-dioxopyrrolidin-1-yl) carbonate plays a pivotal role in crafting sophisticated drug carrier systems. By integrating this compound into carrier molecules, researchers engineer controlled-release mechanisms ensuring steady and effective delivery of therapeutic agents. This precision boosts patient outcomes while minimizing adverse effects, ushering in a new era of targeted and efficient drug delivery.

Surface Modification: The application of (E)-Cyclooct-4-en-1-yl (2,5-dioxopyrrolidin-1-yl) carbonate extends to the realm of surface modification, where it enhances the properties of materials like metals and polymers. By imbuing these materials with functional groups that tweak surface interactions, such as hydrophilicity or hydrophobicity, this compound unlocks a spectrum of applications from biomedical implants to industrial coatings. These tailored modifications are pivotal in optimizing material performance across diverse industries.

Organic Synthesis: A cornerstone in organic synthesis, (E)-Cyclooct-4-en-1-yl (2,5-dioxopyrrolidin-1-yl) carbonate acts as a versatile intermediate, enabling the preparation of complex molecules. Its reactive nature facilitates the introduction of various functional groups, catalyzing the synthesis of a broad array of compounds. This versatility positions it as an indispensable reagent in crafting pharmaceuticals, agrochemicals, and specialty chemicals, underscoring its pivotal role in advancing the frontier of organic chemistry and material science.

1. Comparison of analytical methods for antibody conjugates with application in nuclear imaging - Report from the trenches

Irene V J Feiner, Beatrice Longo, Vanessa Gómez-Vallejo, Javier Calvo, Marion Chomet, Danielle J Vugts, Albert D Windhorst, Daniel Padro, Matteo Zanda, Luka Rejc, Jordi Llop Nucl Med Biol. 2021 Nov-Dec;102-103:24-33.doi: 10.1016/j.nucmedbio.2021.08.001.Epub 2021 Aug 18.

Introduction:Monoclonal antibodies (mAbs) are widely used in nuclear imaging. Radiolabelling with positron emitting radionuclides, typically radiometals, requires the incorporation of a bifunctional chelator for the formation of the radiometal-mAb complex. Additionally, mAbs can be conjugated with small molecules capable to undergo bioorthogonal click reactions in vivo, enabling pre-targeting strategies. The determination of the number of functionalities attached to the mAb is critically important to ensure a good labelling yield or to guarantee pre-targeting efficacy. In this work, we compare three different analytical methods for the assessment of average functionalisation and heterogeneity of the conjugated mAbs. Methods:Two selected mAbs (Trastuzumab and Bevacizumab) were randomly conjugated through lysine residues with 3-10 equivalents p-isothiocyanatobenzyl-desferrioxamine (p-NCS-Bz-DFO) or 20-200 equivalents trans-cyclooctene-N-hydroxysuccinimide ester (TCO-NHS). The DFO- or TCO-to-mAb ratio were determined using three different methods: direct titration (radiometric for DFO-conjugated mAbs, photometric for TCO-conjugated mAbs), MALDI/TOF MS mass analysis (Matrix-Assisted Laser Desorption-Ionization/Time of Flight Mass Spectrometry), and UPLC/ESI-TOF MS mass analysis (Ultra High Performance Liquid Chromatography/Electrospray Ionization-Time of Flight Mass Spectrometry). Results:Radiometric and photometric titrations provided information on the average number of DFO and TCO functionalities per mAb respectively. MALDI/TOF MS provided equivalent results to those obtained by titration, although investigation of the heterogeneity of the resulting mixture was challenging and inaccurate. UPLC/ESI-TOF MS resulted in good peak resolution in the case of DFO-conjugated mAbs, where an accurate discrimination of the contribution of mono-, di- and tri-substituted mAbs could be achieved by mathematical fitting of the spectra. However, UPLC/ESI-TOF MS was unable to discriminate between different conjugates when the smaller TCO moiety was attached to the mAbs.Conclusions:The three techniques offered comparable results in terms of determining the average number of conjugates per mAb. Additionally, UPLC/ESI-TOF MS was able to shed a light on the heterogeneity of the resulting functionalised mAbs, especially in the case of DFO-conjugated mAbs. Finally, while using a single analytical method might not be a reliable way to determine the average functionalisation and assess the heterogeneity of the sample, a combination of these methods could substantially improve the characterization of mAb conjugates.

2. A Pretargeted Imaging Strategy for Immune Checkpoint Ligand PD-L1 Expression in Tumor Based on Bioorthogonal Diels-Alder Click Chemistry

Lin Qiu, Hui Tan, Qingyu Lin, Zhan Si, Wujian Mao, Tingting Wang, Zhequan Fu, Dengfeng Cheng, Hongcheng Shi Mol Imaging Biol. 2020 Aug;22(4):842-853.doi: 10.1007/s11307-019-01441-3.

Purpose:The use of antibodies as tracers requires labeling with isotopes with long half-lives due to their slow pharmacokinetics, which creates prohibitively high radiation dose to non-target organs. Pretargeted methodology could avoid the high radiation exposure due to the slow pharmacokinetics of antibodies. In this investigation, we reported the development of a novel pretargeted single photon emission computed tomography (SPECT) imaging strategy (atezolizumab-TCO/[99mTc]HYNIC-PEG11-Tz) for evaluating immune checkpoint ligand PD-L1 expression in tumor based on bioorthogonal Diels-Alder click chemistry.Procedures:The radioligand [99mTc]HYNIC-PEG11-Tz was achieved by the synthesis of a 6-hydrazinonicotinc acid (HYNIC) modified 1,2,4,5-tetrazine (Tz) and subsequently radiolabeled with technetium-99m (Tc-99m). The stability of [99mTc]HYNIC-PEG11-Tz was evaluated in vitro, and its blood pharmacokinetic test was performed in vivo. Atezolizumab was modified with trans-cyclooctene (TCO). The [99mTc]HYNIC-PEG11-Tz and atezolizumab-TCO interaction was tested in vitro. Pretargeted H1975 cell immunoreactivity binding and saturation binding assays were evaluated. Pretargeted biodistribution and SPECT imaging experiments were performed in H1975 and A549 tumor-bearing modal mice to evaluate the PD-L1 expression level. Results:[99mTc]HYNIC-PEG11-Tz was successfully radiosynthesized with a specific activity of 9.25 MBq/μg and a radiochemical purity above 95 % as confirmed by reversed-phase HPLC (RP-HPLC). [99mTc]HYNIC-PEG11-Tz showed favorable stability in NS, PBS, and FBS and rapid blood clearance in mice. The atezolizumab was modified with TCO-NHS ester to produce a conjugate with an average 6.4 TCO moieties as confirmed by liquid chromatograph-mass spectrometer (LC-MS). Size exclusion HPLC revealed almost complete reaction between atezolizumab-TCO and [99mTc]HYNIC-PEG11-Tz in vitro, with the 1:1 Tz-to-mAb reaction providing a conversion yield of 88.65 ± 1.22 %. Pretargeted cell immunoreactivity binding and saturation binding assays showed high affinity to H1975 cells. After allowing 48 h for accumulation of atezolizumab-TCO in H1975 tumor, pretargeted in vivo biodistribution revealed high uptake of the radiotracer in the tumor with a tumor-to-muscle ratio of 27.51 and tumor-to-blood ratio of 1.91. Pretargeted SPECT imaging delineated the H1975 tumor clearly. Pretargeted biodistribution and SPECT imaging in control groups demonstrated a significantly reduced tracer accumulation in the A549 tumor.Conclusions:We have developed a HYNIC-modified Tz derivative, and the HYNIC-PEG11-Tz was labeled with Tc-99m with a high specific activity and radiochemical purity. [99mTc]HYNIC-PEG11-Tz reacted rapidly and almost completely towards atezolizumab-TCO in vitro with the 1:1 Tz-to-mAb reaction. SPECT imaging using the pretargeted strategy (atezolizumab-TCO/[99mTc]HYNIC-PEG11-Tz) demonstrated high-contrast images for high PD-L1 expression H1975 tumor and a low background accumulation of the probe. The pretargeted imaging strategy is a powerful tool for evaluating PD-L1 expression in xenograft mice tumor models and a potential candidate for translational clinical application.