Synthesis and Evaluation of a Series of 1,2,4,5-Tetrazines for Bioorthogonal Conjugation

Karver, Mark R.; Weissleder, Ralph; Hilderbrand, Scott A.

doi:10.1021/bc200295y

Cited by 384 publications

(497 citation statements)

References 39 publications

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“…3-(p-benzylamino)-1,2,4,5-tetrazine was synthesized according to an established protocol [32]. Briefly, 50 mmol of 4-(aminomethyl)benzonitrile hydrochloride and 150 mmol formamidine acetate were mixed while adding 1 mol of anhydrous hydrazine.…”

Section: -(P-benzylamino)-1245 Tetrazine Synthesismentioning

confidence: 99%

Versatile click alginate hydrogels crosslinked via tetrazine–norbornene chemistry

et al. 2015

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Abstract:Alginate hydrogels are well-characterized, biologically inert materials that are used in many biomedical applications for the delivery of drugs, proteins, and cells. Unfortunately, canonical covalently crosslinked alginate hydrogels are formed using chemical strategies that can be biologically harmful due to their lack of chemoselectivity. In this work we introduce tetrazine and norbornene groups to alginate polymer chains and subsequently form covalently crosslinked click alginate hydrogels capable of encapsulating cells without damaging them. The rapid, bioorthogonal, and specific click reaction is irreversible and allows for easy incorporation of cells with high post-encapsulation viability. The swelling and mechanical properties of the click alginate hydrogel can be tuned via the total polymer concentration and the stoichiometric ratio of the complementary click functional groups. The click alginate hydrogel can be modified after gelation to display cell adhesion peptides for 2D cell culture using thiol-ene chemistry.Furthermore, click alginate hydrogels are minimally inflammatory, maintain structural integrity over several months, and reject cell infiltration when injected subcutaneously in mice. Click alginate hydrogels combine the numerous benefits of alginate hydrogels with powerful bioorthogonal click chemistry for use in tissue engineering applications involving the stable encapsulation or delivery of cells or bioactive molecules.

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Section: -(P-benzylamino)-1245 Tetrazine Synthesismentioning

confidence: 99%

Versatile click alginate hydrogels crosslinked via tetrazine–norbornene chemistry

et al. 2015

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“…The strained dienophiles that have been tested include norbornene, cyclooctyne, cyclopropene, and trans-cyclooctene (TCO), each displaying varying reaction speeds. Modifying Tz substituents has also been shown to affect the reaction speed with TCO, as well as Tz stability in serum [26] . The extremely fast Owing to the potential solubility concerns for the dienephiles, particularly those with ring structures (TCO, cyclooctyne, cyclopropene), we do not recommend high-density modification of the nanoparticles.…”

Section: History Of Developmentmentioning

confidence: 99%

“…The extremely fast Owing to the potential solubility concerns for the dienephiles, particularly those with ring structures (TCO, cyclooctyne, cyclopropene), we do not recommend high-density modification of the nanoparticles. [26].…”

Section: History Of Developmentmentioning

confidence: 99%

Bioorthogonal chemistries for nanomaterial conjugation and targeting

Rahim

Kota

Lee

et al. 2013

Nanotechnology Reviews

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Bioorthogonal chemistries are covalent reaction pairs that proceed in the presence of biological components with complete specificity. A suite of reactions has been described to date that provides scientists and engineers with diverse operational characteristics for different applications. Nanomaterials in particular have benefitted from these new capabilities, resulting in improved coupling efficiencies and multifunctionality. In this review, we will discuss the application of bioorthogonal chemistries to different nanomaterial systems, highlighting the advantages and limitations for use in bioconjugation. We will also describe how recent improvements in the reaction speed of catalyst-free bioorthogonal chemistries have enabled the successful coupling of nanomaterials directly to live cells. Using a recently developed reaction pair, tetrazine and trans -cyclooctene, the direct covalent coupling to cells has been shown to occur on time-scales that are relevant for biological studies and diagnostic applications and can even amplify nanomaterial binding greater than tenfold relative to traditional immunoconjugates. This powerful technique still maintains exquisite specificity, however, yielding robust results in clinical diagnostic applications using human tissue and blood samples. Future work will likely focus on further advancement of the in situ amplification technique, such as increasing nanomaterial binding, enabling multiplexed detection through the use of orthogonal reaction systems and extension to applications in vivo .

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“…The functionalization was exemplarily carried out with the well investigated cRGD [151][152][153] , a small molecule which acts as a ligand for specific binding to the    5 integrin receptor, involved in neoangiogenic and metastasis processes [154][155][156] . The characteristics of the used DAR inv -allowed a bioorthogonal click reaction strategy [157][158][159] for a bridge formation between inorganic surfaces and biological active molecules 160 .…”

Section: Total Synthesis Of Cannabinol and Derivativesmentioning

confidence: 99%

Untitled

2013

IJPSR

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ABSTRACT:Here, we review the development of prospective image processing systems in molecular diagnostics and of pharmacologically active ingredients for patient-specific therapeutic approaches. These projects require not only high demands on quality, safety, and specificity but also, rapid, efficient and irreversible ligation routes during the synthesis of future pharmaceuticals. The Diels-Alder ligation reaction with inverse electron demand (DAR inv ) is an eligible technology not restricted to medical applications, but valuable in selective modification by functionalization of polymers, organic and inorganic surfaces and micro arrays. Additionally, the DAR inv technology is considered as an attractive strategy-platform for efficient syntheses of promising pharmacologically active components and derivatives of natural molecules with an optimized therapeutic index. We like to encourage scientists working with the brilliant concept of Sharpless"s "Click chemistry", to intensify their research with this valuable DAR inv technology able to open the door for regioselective, stereospecific, and bioorthogonal exigent syntheses of substances of highest quality inconceivable so far.

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Synthesis and Evaluation of a Series of 1,2,4,5-Tetrazines for Bioorthogonal Conjugation

Cited by 384 publications

References 39 publications

Versatile click alginate hydrogels crosslinked via tetrazine–norbornene chemistry

Versatile click alginate hydrogels crosslinked via tetrazine–norbornene chemistry

Bioorthogonal chemistries for nanomaterial conjugation and targeting

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