I can see clearly now: Bicyclo[6.1.0]non-4-yne, an easily prepared, symmetrical cycloalkyne, displays excellent reaction kinetics in strain-promoted cycloaddition reactions with azides and nitrones (see scheme). Highly specific protein modifications are demonstrated vitro subcellular-resolved imaging of glycan expression was achieved metastatic melanoma cells during invasive migration into three-dimensional collagen lattices.

A strained aza-dibenzocyclooctyne was prepared via a high-yielding synthetic route. Copper-free, strain-promoted click reaction with azides showed excellent kinetics, and functionalised aza-cyclooctyne applied in fast efficient PEGylation of enzymes.

The structural complexity of molecules isolated from biological sources has always served as an inspiration for organic chemists. Since the first synthesis a natural product, urea, chemists have been challenged to prepare exact copies structures in laboratory. As result, broad repertoire synthetic transformations developed over years. It is now feasible synthesize enormous complexity, and also with less but prodigious societal impact, such nylon, TNT, polystyrene, statins, estradiol, XTC,...

The 1,3-dipolar cycloaddition of azides with ring-strained alkynes is one the few bioorthogonal reactions suitable for specific biomolecule labeling in complex biological systems. Nevertheless, azide-independent proteins by strained can occur to a varying extent, thereby limiting sensitivity assays based on strain-promoted azide–alkyne (SPAAC). In this study, subset three cyclooctynes, dibenzocyclooctyne (DIBO), azadibenzocyclooctyne (DIBAC), and bicyclo[6.1.0]nonyne (BCN), was used evaluate...

A robust, generally applicable, nongenetic technology is presented to convert monoclonal antibodies into stable and homogeneous ADCs. Starting from a native (nonengineered) mAb, chemoenzymatic protocol allows for the highly controlled attachment of any given payload N-glycan residing at asparagine-297, based on two-stage process: first, enzymatic remodeling (trimming tagging with azide), followed by ligation copper-free click chemistry. The technology, termed GlycoConnect, applicable IgG...

Quicker and slicker: An efficient metal-free 1,3-dipolar cycloaddition of dibenzocyclooctynes with nitrones proceeded rate constants up to 39 M−1 s−1, or 300 times faster than similar reactions azides. This strategy is useful for the site-specific N-terminal modification peptides proteins (see scheme). The bioorthogonal chemical reporter emerging as a versatile method labeling biomolecules, such nucleic acids, lipids, carbohydrates, proteins.1 In this approach, an abiotic functionality...

Biohybrid amphiphiles have been prepared from terminal azide functionalised polystyrene and an alkyne peptide or protein via a Cu(I) catalysed Huisgen [3 + 2] dipolar cycloaddition reaction.

Who needs copper? There is a strong demand for ligation reactions that proceed spontaneously, selectively, and under physiological conditions. To meet these criteria, we used trifluoromethyl-substituted oxanorbornadienes in with various azides, achieved an elegant tandem [3+2] cycloaddition–retro-Diels–Alder reaction forms stable 1,2,3-triazole-linked bioconjugates (see scheme). Supporting information this article available on the WWW...

[structure: see text] An expedient, high-yielding synthesis of two types triazole-linked glycopeptides is described. These novel and stable glycopeptide mimics were prepared via Cu(I)-catalyzed [3 + 2] cycloaddition either azide-functionalized glycosides acetylenic amino acids or azide-containing acids.

Abstract Several important reactions in organic chemistry thrive on stoichiometric formation of phosphine oxides from phosphines. To avoid the resulting burden waste and purification, cyclic were evaluated for new catalytic based situ regeneration. First, ease silane‐mediated reduction a range was explored. In addition, compatibility silanes with electrophilic halogen donors determined application Appel reaction dibenzophosphole oxide. Under optimized conditions, alcohols effectively...

Abstract Visualizing biomolecules by fluorescent tagging is a powerful method for studying their behaviour and function inside cells. We prepared genetically encoded an unnatural amino acid (UAA) that features bicyclononyne moiety. This UAA offered exceptional reactivity in strain‐promoted azide–alkyne cycloadditions. Kinetic measurements revealed the reacted also remarkably fast inverse‐electron‐demand Diels–Alder cycloaddition with tetrazine‐conjugated dyes. Genetic encoding of new...

Cancer cells decorate their surface with a dense layer of sialylated glycans by upregulating the expression sialyltransferases and other glycogenes. Although sialic acids play vital role in many biologic processes, hypersialylation particular has been shown to contribute cancer cell progression metastasis. Accordingly, selective strategies interfere acid synthesis might offer powerful approach therapy. In present study, we assessed potential recently developed fluorinated analogue...

Spannungslösend: Das leicht herstellbare, symmetrische Cycloalkin Bicyclo[6.1.0]non-4-in zeigt hervorragende Reaktionskinetiken bei spannungsgetriebenen Cycloadditionen mit Aziden und Nitronen (siehe Schema). In vitro wurden hoch spezifische Proteinmodifizierungen nachgewiesen. Zudem gelang subzellulärer Auflösung die Bildgebung der Glycanexpression in metastatischen Melanomzellen während invasiven Migration dreidimensionale Collagengitter. The advent of chemical biology tools for imaging...

Treatment of oximes with hypervalent iodine leads to substituted isoxazolesvia rapid formation nitrile oxides. Reaction terminal alkynes led a series 3,5-disubstituted isoxazoles complete regioselectivity and high yield, in procedure mild enough prepare range nucleoside peptide conjugates. Exceptionally reaction rates were found for the 3,4,5-trisubstituted from cyclic alkyne.

Abstract The first Staudinger reduction that is catalytic in phosphine has been developed, showing excellent yields and functional group selectivity. To this end we utilised dibenzophosphole catalysts mild situ of the intermediate iminophosphoranes. We could avoid necessity water during reduction, obtained no oxides as waste thus enabled facile purification product. A range azides was converted into amines with good to high tolerance.

A main challenge in the area of bioconjugation is to devise reactions that are both activatable and fast. Here, we introduce a temporally controlled reaction between cyclooctynes 1,2-quinones, induced by facile oxidation 1,2-catechols. This so-called strain-promoted oxidation-controlled cyclooctyne–1,2-quinone cycloaddition (SPOCQ) shows remarkably high rate when performed with bicyclononyne (BCN), outcompeting well-known azides BCN 3 orders magnitude, thereby allowing new level...

Genetically encoded tyrosine (Y-tag) can be utilized as a latent anchor for inducible and site-selective conjugation. Upon oxidation of with mushroom tyrosinase, strain-promoted cycloaddition (SPOCQ) the resulting 1,2-quinone various bicyclo[6.1.0]nonyne (BCN) derivatives led to efficient The method was applied fluorophore labeling laminarinase A site-specific preparation an antibody–drug conjugate.