共查询到20条相似文献,搜索用时 139 毫秒
1.
Enrique Gil de Montes Dr. Alena Istrate Dr. Claudio D. Navo Dr. Ester Jiménez-Moreno Emily A. Hoyt Dr. Francisco Corzana Prof. Inmaculada Robina Dr. Gonzalo Jiménez-Osés Dr. Antonio J. Moreno-Vargas Dr. Gonçalo J. L. Bernardes 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(15):6255-6259
An azanorbornadiene bromovinyl sulfone reagent for cysteine-selective bioconjugation has been developed. Subsequent reaction with dipyridyl tetrazine leads to bond cleavage and formation of a pyrrole-linked conjugate. The latter involves ligation of the tetrazine to the azanorbornadiene-tagged protein through inverse electron demand Diels–Alder cycloaddition with subsequent double retro-Diels–Alder reactions to form a stable pyrrole linkage. The sequence of site-selective bioconjugation followed by bioorthogonal bond cleavage was efficiently employed for the labelling of three different proteins. This method benefits from easy preparation of these reagents, selectivity for cysteine, and stability after reaction with a commercial tetrazine, which has potential for the routine preparation of protein conjugates for chemical biology studies. 相似文献
2.
Bruno L. Oliveira Zijian Guo Omar Boutureira Ana Guerreiro Gonzalo Jimnez‐Oss Gonalo J. L. Bernardes 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2016,128(47):14903-14907
The unstrained S‐allyl cysteine amino acid was site‐specifically installed on apoptosis protein biomarkers and was further used as a chemical handle and ligation partner for 1,2,4,5‐tetrazines by means of an inverse‐electron‐demand Diels–Alder reaction. We demonstrate the utility of this minimal handle for the efficient labeling of apoptotic cells using a fluorogenic tetrazine dye in a pre‐targeting approach. The small size, easy chemical installation, and selective reactivity of the S‐allyl handle towards tetrazines should be readily extendable to other proteins and biomolecules, which could facilitate their labeling within live cells. 相似文献
3.
A Minimal,Unstrained S‐Allyl Handle for Pre‐Targeting Diels–Alder Bioorthogonal Labeling in Live Cells 下载免费PDF全文
Dr. Bruno L. Oliveira Zijian Guo Dr. Omar Boutureira Ana Guerreiro Dr. Gonzalo Jiménez‐Osés Dr. Gonçalo J. L. Bernardes 《Angewandte Chemie (International ed. in English)》2016,55(47):14683-14687
The unstrained S‐allyl cysteine amino acid was site‐specifically installed on apoptosis protein biomarkers and was further used as a chemical handle and ligation partner for 1,2,4,5‐tetrazines by means of an inverse‐electron‐demand Diels–Alder reaction. We demonstrate the utility of this minimal handle for the efficient labeling of apoptotic cells using a fluorogenic tetrazine dye in a pre‐targeting approach. The small size, easy chemical installation, and selective reactivity of the S‐allyl handle towards tetrazines should be readily extendable to other proteins and biomolecules, which could facilitate their labeling within live cells. 相似文献
4.
《Journal of heterocyclic chemistry》2018,55(6):1489-1493
Syntheses of pyridazine and pyrrole analogues of 2‐aminotetralin starting from 3‐cyclohexene‐1‐carboxylic acid are reported. All syntheses involve the following key steps: Curtius rearrangement for amine functionality, inverse electron demand Diels–Alder addition with 1,2,4,5‐tetrazine for pyridazine ring synthesis, and pyridazine‐to‐pyrrole ring contraction for pyrrole ring formation. 相似文献
5.
Synthesis and Reactivity Comparisons of 1‐Methyl‐3‐Substituted Cyclopropene Mini‐tags for Tetrazine Bioorthogonal Reactions 下载免费PDF全文
Dr. Jun Yang Dr. Yong Liang Dr. Jolita Šečkutė Prof. K. N. Houk Prof. Neal K. Devaraj 《Chemistry (Weinheim an der Bergstrasse, Germany)》2014,20(12):3365-3375
Substituted cyclopropenes have recently attracted attention as stable “mini‐tags” that are highly reactive dienophiles with the bioorthogonal tetrazine functional group. Despite this interest, the synthesis of stable cyclopropenes is not trivial and their reactivity patterns are poorly understood. Here, the synthesis and comparison of the reactivity of a series of 1‐methyl‐3‐substituted cyclopropenes with different functional handles is described. The rates at which the various substituted cyclopropenes undergo Diels–Alder cycloadditions with 1,2,4,5‐tetrazines were measured. Depending on the substituents, the rates of cycloadditions vary by over two orders of magnitude. The substituents also have a dramatic effect on aqueous stability. An outcome of these studies is the discovery of a novel 3‐amidomethyl substituted methylcyclopropene tag that reacts twice as fast as the fastest previously disclosed 1‐methyl‐3‐substituted cyclopropene while retaining excellent aqueous stability. Furthermore, this new cyclopropene is better suited for bioconjugation applications and this is demonstrated through using DNA templated tetrazine ligations. The effect of tetrazine structure on cyclopropene reaction rate was also studied. Surprisingly, 3‐amidomethyl substituted methylcyclopropene reacts faster than trans‐cyclooctenol with a sterically hindered and extremely stable tert‐butyl substituted tetrazine. Density functional theory calculations and the distortion/interaction analysis of activation energies provide insights into the origins of these reactivity differences and a guide to the development of future tetrazine coupling partners. The newly disclosed cyclopropenes have kinetic and stability advantages compared to previously reported dienophiles and will be highly useful for applications in organic synthesis, bioorthogonal reactions, and materials science. 相似文献
6.
Clve D. Mboyi Delphine Vivier Ahmad Daher Paul Fleurat‐Lessard Hlne Cattey Charles H. Devillers Claire Bernhard Franck Denat Julien Roger Jean‐Cyrille Hierso 《Angewandte Chemie (International ed. in English)》2020,59(3):1149-1154
Click chemistry at a tetrazine core is useful for bioorthogonal labeling and crosslinking. Introduced here are two new classes of doubly clickable s‐aryl tetrazines synthesized by Cu‐catalyzed cross‐coupling. Homocoupling of o‐brominated s‐aryl tetrazines leads to bis(tetrazine)s structurally characterized by tetrazine cores arranged face‐to‐face. [N]8 π‐stacking interactions are essential to the conformation. Upon inverse electron demand Diels–Alder (iEDDA) cycloaddition, the bis(tetrazine)s produce a unique staple structure. The o‐azidation of s‐aryl tetrazines introduces a second proximal intermolecular clickable function that leads to double click chemistry opportunities. The stepwise introduction of fluorophores and then iEDDA cycloaddition, including bioconjugation to antibodies, was achieved on this class of tetrazines. This method extends to (thio)etherification, phosphination, trifluoromethylation and the introduction of various bioactive nitrogen‐based heterocycles. 相似文献
7.
Tetrazine Click Chemistry for the Modification of 1‐Hydroxy‐1,1‐methylenebisphosphonic Acids: Towards Bio‐orthogonal Functionalization of Gold Nanoparticles 下载免费PDF全文
Romain Aufaure Dr. Julie Hardouin Prof. Nadine Millot Prof. Laurence Motte Dr. Yoann Lalatonne Dr. Erwann Guénin 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(45):16022-16027
Inverse electron demand Diels–Alder (iEDDA) was evaluated for the functionalization of gold nanoparticles. The reaction was first modelled with the free coating molecule 1‐hydroxy‐1,1‐methylenebisphosphonate bearing an alkene functionality (HMBPene). A model tetrazine 3,6‐dipyridin‐2‐yl‐1,2,4,5‐tetrazine (pyTz) was used, kinetic of the reaction was calculated and coupling products were analysed by NMR and HRMS. The reaction was then transposed at the nanoparticle surface. Gold nanoparticles bearing an alkene functionality were obtained using a one‐pot methodology with HMBPene and the tetrazine click chemistry was evaluated at their surface using pyTz. The successful coupling was assessed by XPS measurements. This click‐methodology was extended to the conjugation of a NIR probe at the NP surface. 相似文献
8.
He Li Joo Conde Ana Guerreiro Gonalo J. L. Bernardes 《Angewandte Chemie (International ed. in English)》2020,59(37):16023-16032
The bioorthogonal inverse‐electron‐demand Diels–Alder (IEDDA) cleavage reaction between tetrazine and trans‐cyclooctene (TCO) is a powerful way to control the release of bioactive agents and imaging probes. In this study, a pretargeted activation strategy using single‐walled carbon nanotubes (SWCNTs) that bear tetrazines (TZ@SWCNTs) and a TCO‐caged molecule was used to deliver active effector molecules. To optimize a turn‐on signal by using in vivo fluorescence imaging, we developed a new fluorogenic near‐infrared probe that can be activated by bioorthogonal chemistry and image tumours in mice by caging hemicyanine with TCO (tHCA). With our pretargeting strategy, we have shown selective doxorubicin prodrug activation and instantaneous fluorescence imaging in living cells. By combining a tHCA probe and a pretargeted bioorthogonal approach, real‐time, non‐invasive tumour visualization with a high target‐to‐background ratio was achieved in a xenograft mice tumour model. The combined advantages of enhanced stability, kinetics and biocompatibility, and the superior pharmacokinetics of tetrazine‐functionalised SWCNTs could allow application of targeted bioorthogonal decaging approaches with minimal off‐site activation of fluorophore/drug. 相似文献
9.
Mark A. R. de Geus Elmer Maurits Alexi J. C. Sarris Thomas Hansen Max S. Kloet Kiki Kamphorst Dr. Wolter ten Hoeve Dr. Marc S. Robillard Dr. Andrea Pannwitz Dr. Sylvestre A. Bonnet Dr. Jeroen D. C. Codée Dr. Dmitri V. Filippov Prof. Herman S. Overkleeft Dr. Sander I. van Kasteren 《Chemistry (Weinheim an der Bergstrasse, Germany)》2020,26(44):9900-9904
The inverse electron demand Diels–Alder pyridazine elimination reaction between tetrazines and allylic substituted trans-cyclooctenes (TCOs) is a key player in bioorthogonal bond cleavage reactions. Determining the rate of elimination of alkylamine substrates has so far proven difficult. Here, we report a fluorogenic tool consisting of a TCO-linked EDANS fluorophore and a DABCYL quencher for accurate determination of both the click and release rate constants for any tetrazine at physiologically relevant concentrations. 相似文献
10.
Katherine A. Horner Dr. Nathalie M. Valette Dr. Michael E. Webb 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(41):14376-14381
Strain‐promoted inverse electron‐demand Diels–Alder cycloaddition (SPIEDAC) reactions between 1,2,4,5‐tetrazines and strained dienophiles, such as bicyclononynes, are among the fastest bioorthogonal reactions. However, the synthesis of 1,2,4,5‐tetrazines is complex and can involve volatile reagents. 1,2,4‐Triazines also undergo cycloaddition reactions with acyclic and unstrained dienophiles at elevated temperatures, but their reaction with strained alkynes has not been described. We postulated that 1,2,4‐triazines would react with strained alkynes at low temperatures and therefore provide an alternative to the tetrazine cycloaddition reaction for use in in vitro or in vivo labelling experiments. We describe the synthesis of a 1,2,4‐triazin‐3‐ylalanine derivative fully compatible with the fluorenylmethyloxycarbonyl (Fmoc) strategy for peptide synthesis and demonstrate its reaction with strained bicyclononynes at 37 °C with rates comparable to the reaction of azides with the same substrates. The synthetic route to triazinylalanine is readily adaptable to late‐stage functionalization of other probe molecules, and the 1,2,4‐triazine‐SPIEDAC therefore has potential as an alternative to tetrazine cycloaddition for applications in cellular and biochemical studies. 相似文献
11.
Bioinspired Intramolecular Diels–Alder Reaction: A Rapid Access to the Highly‐Strained Cyclopropane‐Fused Polycyclic Skeleton 下载免费PDF全文
Prof. Dr. Shifa Zhu Zhengjiang Guo Zhipeng Huang Prof. Dr. Huanfeng Jiang 《Chemistry (Weinheim an der Bergstrasse, Germany)》2014,20(9):2425-2430
A bioinsipred gold‐catalyzed tandem Diels–Alder/Diels–Alder reaction of an enynal and a 1,3‐diene, forming the highly‐strained benzotricyclo[3.2.1.02,7]octane skeleton, was reported. In contrast, a Diels–Alder/Friedel–Crafts tandem reaction occurred instead when silver salts were used as the catalyst. Although both reactions experienced the similar Diels–Alder reaction of a pyrylium intermediate with a 1,3‐diene, they have different reaction mechanisms. The former proceeded with a stepwise Diels–Alder reaction, while the latter one with a concerted one. 相似文献
12.
Zixin Chen Min Chen Kaixiang Zhou Jianghong Rao 《Angewandte Chemie (International ed. in English)》2020,59(20):7864-7870
The pre‐targeted imaging of enzyme activity has not been reported, likely owing to the lack of a mechanism to retain the injected substrate in the first step for subsequent labeling. Herein, we report the use of two bioorthogonal reactions—the condensation reaction of aromatic nitriles and aminothiols and the inverse‐electron demand Diels–Alder reaction between tetrazine and trans‐cyclooctene (TCO)—to develop a novel strategy for pre‐targeted imaging of the activity of proteases. The substrate probe ( TCO‐C‐SNAT4 ) can be selectively activated by an enzyme target (e.g. caspase‐3/7), which triggers macrocyclization and subsequent in situ self‐assembly into nanoaggregates retained at the target site. The tetrazine‐imaging tag conjugate labels TCO in the nanoaggregates to generate selective signal retention for imaging in vitro, in cells, and in mice. Owing to the decoupling of enzyme activation and imaging tag immobilization, TCO‐C‐SNAT4 can be repeatedly injected to generate and accumulate more TCO‐nanoaggregates for click labeling. 相似文献
13.
Peter Wonneberger Nils Knig Fabian B. Kraft Menyhrt B. Srosi Evamarie Hey‐Hawkins 《Angewandte Chemie (International ed. in English)》2019,58(10):3208-3211
The unprecedented phospha‐aza‐Diels–Alder reaction between an activated electron‐poor imine and 2H‐phospholes yields 1‐phospha‐2‐azanorbornenes in a highly chemoselective and moderately diastereoselective reaction. The intermediate 2H‐phospholes, which act as dienes, are formed in situ from the corresponding 1H‐phospholes. Theoretical calculations confirm that the phospha‐aza‐Diels–Alder reaction is of normal electron demand. The reactive P?N bond in 1‐phospha‐2‐azanorbornenes can be cleaved by nucleophiles leading to the formation of 2,3‐dihydrophospholes. 相似文献
14.
New Red‐Emitting Tetrazine‐Phenoxazine Fluorogenic Labels for Live‐Cell Intracellular Bioorthogonal Labeling Schemes 下载免费PDF全文
Gergely Knorr Eszter Kozma Dr. András Herner Dr. Edward A. Lemke Dr. Péter Kele 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(26):8972-8979
The synthesis of a set of tetrazine‐bearing fluorogenic dyes suitable for intracellular labeling of proteins in live cells is presented. The red excitability and emission properties ensure minimal autofluorescence, while through‐bond energy‐transfer‐based fluorogenicity reduces nonspecific background fluorescence of unreacted dyes. The tetrazine motif efficiently quenches fluorescence of the phenoxazine core, which can be selectively turned on chemically upon bioorthogonal inverse‐electron‐demand Diels–Alder reaction with proteins modified genetically with strained trans‐cyclooctenes. 相似文献
15.
Cuiju Zhu Rositha Kuniyil Lutz Ackermann 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(16):5392-5396
Complexity‐increasing Domino reactions comprising C?H allenylation, a Diels–Alder reaction, and a retro‐Diels–Alder reaction were realized by a versatile catalyst derived from earth‐abundant, non‐toxic manganese. The C?H activation/Diels–Alder/retro‐Diels–Alder alkyne annulation sequence provided step‐economical access to valuable indolone alkaloid derivatives through a facile organometallic C?H activation manifold with transformable pyridines. 相似文献
16.
Catalytic Asymmetric Diels–Alder Reaction of Quinone Imine Ketals: A Site‐Divergent Approach 下载免费PDF全文
Dr. Takuya Hashimoto Hiroki Nakatsu Prof.Dr. Keiji Maruoka 《Angewandte Chemie (International ed. in English)》2015,54(15):4617-4621
The catalytic asymmetric Diels–Alder reaction of quinone imine ketals with diene carbamates catalyzed by axially chiral dicarboxylic acids is reported herein. A variety of primary and secondary alkyl‐substituted quinone derivatives which have not been applied in previous asymmetric quinone Diels–Alder reactions could be employed using this method. More importantly, we succeeded in developing a strategy to divert the reaction site in unsymmetrical 3‐alkyl quinone imine ketals from the inherently favored unsubstituted C?C bond to the disfavored alkyl‐substituted C?C bond. 相似文献
17.
Marc‐Andr Kasper Maria Glanz Andreas Stengl Martin Penkert Simon Klenk Tom Sauer Dominik Schumacher Jonas Helma Eberhard Krause M. Cristina Cardoso Heinrich Leonhardt Christian P. R. Hackenberger 《Angewandte Chemie (International ed. in English)》2019,58(34):11625-11630
We describe a new technique in protein synthesis that extends the existing repertoire of methods for protein modification: A chemoselective reaction that induces reactivity for a subsequent bioconjugation. An azide‐modified building block reacts first with an ethynylphosphonite through a Staudinger‐phosphonite reaction (SPhR) to give an ethynylphosphonamidate. The resulting electron‐deficient triple bond subsequently undergoes a cysteine‐selective reaction with proteins or antibodies. We demonstrate that ethynylphosphonamidates display excellent cysteine‐selective reactivity combined with superior stability of the thiol adducts, when compared to classical maleimide linkages. This turns our technique into a versatile and powerful tool for the facile construction of stable functional protein conjugates. 相似文献
18.
A simple route for the preparation of 3,4,6-substituted pyridazines is described by using Tebbe olefination of esters then Diels–Alder reaction of the resulting enol ethers with tetrazine. 相似文献
19.
Reactivity of 4‐Phenyl‐1,2,4‐triazoline‐3,5‐dione and Diethylazocarboxylate in [4+2]‐Cycloaddition and Ene Reactions: Solvent,Temperature, and High‐Pressure Influence on the Reaction Rate 下载免费PDF全文
Vladimir D. Kiselev Dmitry A. Kornilov Ilzida I. Lekomtseva Alexander I. Konovalov 《国际化学动力学杂志》2015,47(5):289-301
We have studied the solvent, temperature, and pressure influences on the reaction rates of cyclic and acyclic N=N bonds in the Diels–Alder and ene reactions. The transfer from N‐phenylmaleimide ( 9 ) to a structural analogue, 4‐phenyl‐1,2,4‐triazoline‐3,5‐dione ( 2 ), is accompanied by the rate increase in five to six orders of magnitude in the Diels–Alder reactions with cyclopentadiene ( 4 ) and 9,10‐dimethylanthracene ( 5 ), whereas the transfer from dimethyl fumarate ( 10 ) to diethyl azodicarboxylate ( 1 ) increases only in one to two orders of magnitude. The ratio of the reaction rate constants ( 2 + 4 )/( 1 + 4 ) is very large (5.2 × 107) and almost the same (5.3 × 107) as in the ene reactions with tetramethylethylene ( 7 ), ( 2 + 7 )/( 1 + 7 ). It has been observed that the N=N bond in reagent 2 has strong electrophilic, and its N–N moiety in the transition state has nucleophilic properties, which results from the analysis of the solvation enthalpy transfer of reagents, activated complex, and adduct in the Diels–Alder reaction of 2 with anthracene 22 . 相似文献
20.
Dr. Ulrike Rieder Prof. Dr. Nathan W. Luedtke 《Angewandte Chemie (International ed. in English)》2014,53(35):9168-9172
5‐Vinyl‐2′‐deoxyuridine (VdU) is the first reported metabolic probe for cellular DNA synthesis that can be visualized by using an inverse electron demand Diels–Alder reaction with a fluorescent tetrazine. VdU is incorporated by endogenous enzymes into the genomes of replicating cells, where it exhibits reduced genotoxicity compared to 5‐ethynyl‐2′‐deoxyuridine (EdU). The VdU–tetrazine ligation reaction is rapid (k≈0.02 M ?1 s?1) and chemically orthogonal to the alkyne–azide “click” reaction of EdU‐modified DNA. Alkene–tetrazine ligation reactions provide the first alternative to azide–alkyne click reactions for the bioorthogonal chemical labeling of nucleic acids in cells and facilitate time‐resolved, multicolor labeling of DNA synthesis. 相似文献