Site-specific C-functionalization of free-(NH) peptides and glycine derivatives via direct C-H bond functionalization.
Ontology highlight
ABSTRACT:
SUBMITTER: Zhao L
PROVIDER: S-EPMC2649206 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Cyclic amines are ubiquitous core structures of bioactive natural products and pharmaceutical drugs. Although the site-selective abstraction of C-H bonds is an attractive strategy for preparing valuable functionalized amines from their readily available parent heterocycles, this approach has largely been limited to substrates that require protection of the amine nitrogen atom. In addition, most methods rely on transition metals and are incompatible with the presence of amine N-H bonds. Here we introduce a protecting-group-free approach for the ?-functionalization of cyclic secondary amines. An operationally simple one-pot procedure generates products via a process that involves intermolecular hydride transfer to generate an imine intermediate that is subsequently captured by a nucleophile, such as an alkyl or aryl lithium compound. Reactions are regioselective and stereospecific and enable the rapid preparation of bioactive amines, as exemplified by the facile synthesis of anabasine and (-)-solenopsin A.
| S-EPMC5942596 | biostudies-literature
Project description:We have used the well-accepted and easily available 2-[(18)F]fluoro-2-deoxyglucose ([(18)F]FDG) positron emission tomography (PET) tracer as a prosthetic group for synthesis of (18)F-labeled peptides. We herein report the synthesis of [(18)F]FDG-RGD ((18)F labeled linear RGD) and [(18)F]FDG-cyclo(RGD(D)YK) ((18)F labeled cyclic RGD) as examples of the use of [(18)F]FDG. We have successfully prepared [(18)F]FDG-RGD and [(18)F]FDG-cyclo(RGD(D)YK) in 27.5% and 41% radiochemical yields (decay corrected) respectively. The receptor binding affinity study of FDG-cyclo(RGD(D)YK) for integrin alpha(v)beta(3), using alpha(v)beta(3) positive U87MG cells confirmed a competitive displacement with (125)I-echistatin as a radioligand. The IC(50) value for FDG-cyclo(RGD(D)YK) was determined to be 0.67 +/- 0.19 muM. High-contrast small animal PET images with relatively moderate tumor uptake were observed for [(18)F]FDG-RGD and [(18)F]FDG-cyclo(RGD(D)YK) as PET probes in xenograft models expressing alpha(v)beta(3) integrin. In conclusion, we have successfully used [(18)F]FDG as a prosthetic group to prepare (18)F]FDG-RGD and [(18)F]FDG-cyclic[RGD(D)YK] based on a simple one-step radiosynthesis. The one-step radiosynthesis methodology consists of chemoselective oxime formation between an aminooxy-functionalized peptide and [(18)F]FDG. The results have implications for radiolabeling of other macromolecules and would lead to a very simple strategy for routine preclinical and clinical use.
| S-EPMC2765576 | biostudies-literature
Project description:An efficient method is reported for the preparation of multicyclic pyridines and quinolines by a rhodium-catalyzed intramolecular C-H bond functionalization process. The method shows good scope for branched and unbranched alkyl substituents on the pyridine ring and at the R position of the tethered alkene group. Starting materials capable of undergoing olefin isomerization to provide terminal 1,1-disubstituted alkenes also proved to be effective substrates.
| S-EPMC2892546 | biostudies-literature
Project description:The development of a novel intermolecular oxidative amination reaction, a synthetic transformation that involves the simultaneous functionalization of both a N-H and C-H bond, is described. The process, which is mediated by an I(III) oxidant and contains no metal catalysts, provides a rapid and green method for synthesizing protected anilines from simple arenes and phthalimide. Mechanistic investigations indicate that the reaction proceeds via nucleophilic attack of the phthalimide on an aromatic radical cation, as opposed to the electrophilic aromatic amination that has been reported for other I(III) amination reactions. The application of this new reaction to the synthesis of a variety of substituted aniline derivatives is demonstrated.
| S-EPMC3233640 | biostudies-literature
Project description:Biologics, such as antibody-drug conjugates, are becoming mainstream therapeutics. Consequently, methods to functionalize biologics without disrupting their native properties are essential for identifying, characterizing, and translating candidate biologics from the bench to clinical practice. Here, we present a method for site-specific, carboxy-terminal modification of single-chain antibody fragments (scFvs). ScFvs displayed on the surface of yeast were isolated and functionalized by combining intein-mediated expressed protein ligation (EPL) with inverse electron-demand Diels-Alder (IEDDA) cycloaddition using a styrene-tetrazine pair. The high thiol concentration required to trigger EPL can hinder the subsequent chemoselective ligation reactions; therefore, the EPL reaction was used to append styrene to the scFv, limiting tetrazine exposure to damaging thiols. Subsequently, the styrene-functionalized scFv was reacted with tetrazine-conjugated compounds in an IEDDA cycloaddition to generate functionalized scFvs that retain their native binding activity. Rapid functionalization of yeast surface-derived scFv in a site-directed manner could find utility in many downstream laboratory and preclinical applications.
| S-EPMC5963889 | biostudies-literature
Project description:Carbon micro- and nanoelectrodes fabricated by carbon microelectromechanical systems (carbon MEMS) are increasingly used in various biosensors and supercapacitor applications. Surface modification of as-produced carbon electrodes with oxygen functional groups is sometimes necessary for biofunctionalization or to improve electrochemical properties. However, conventional surface treatment methods have a limited ability for selective targeting of parts of a surface area for surface modification without using complex photoresist masks. Here, we report microplasma direct writing as a simple, low-cost, and low-power technique for site-selective plasma patterning of carbon MEMS electrodes with oxygen functionalities. In microplasma direct writing, a high-voltage source generates a microplasma discharge between a microelectrode tip and a target surface held at atmospheric pressure. In our setup, water vapor acts as an ionic precursor for the carboxylation and hydroxylation of carbon surface atoms. Plasma direct writing increases the oxygen content of an SU-8-derived pyrolytic carbon surface from ~3 to 27% while reducing the carbon-to-oxygen ratio from 35 to 2.75. Specifically, a microplasma treatment increases the number of carbonyl, carboxylic, and hydroxyl functional groups with the largest increase observed for carboxylic functionalities. Furthermore, water microplasma direct writing improves the hydrophilicity and the electrochemical performance of carbon electrodes with a contact-angle change from ~90° to ~20°, a reduction in the anodic peak to cathodic peak separation from 0.5 V to 0.17 V, and a 5-fold increase in specific capacitance from 8.82 mF∙cm-2 to 46.64 mF∙cm-2. The plasma direct-writing technology provides an efficient and easy-to-implement method for the selective surface functionalization of carbon MEMS electrodes for electrochemical and biosensor applications.
| S-EPMC6859161 | biostudies-literature
Project description:Labeling of native proteins invites interest from diverse segments of science. However, there remains the significant unmet challenge in precise labeling at a single site of a protein. Here, we report the site-specific labeling of natural or easy-to-engineer N-terminus Gly in proteins with remarkable efficiency and selectivity. The method generates a latent nucleophile from N-terminus imine that reacts with an aldehyde to deliver an aminoalcohol under physiological conditions. It differentiates N-Gly as a unique target amongst other proteinogenic amino acids. The method allows single-site labeling of proteins in isolated form and extends to lysed cells. It administers an orthogonal aldehyde group primed for late-stage tagging with an affinity tag, 19F NMR probe, and a fluorophore. A user-friendly protocol delivers analytically pure tagged proteins. The mild reaction conditions do not alter the structure and function of the protein. The cellular uptake of fluorophore-tagged insulin and its ability to activate the insulin-receptor mediated signaling remains unperturbed.
| S-EPMC6557831 | biostudies-other
Project description:Biotechnological production is a powerful tool to design materials with customized properties. The aim of this work was to apply designed spider silk proteins to produce Janus fibers with two different functional sides. First, functionalization was established through a cysteine-modified silk protein, ntagCys eADF4(κ16). After fiber spinning, gold nanoparticles (AuNPs) were coupled via thiol-ene click chemistry. Significantly reduced electrical resistivity indicated sufficient loading density of AuNPs on such fiber surfaces. Then, Janus fibers were electrospun in a side-by-side arrangement, with "non-functional" eADF4(C16) on the one and "functional" ntagCys eADF4(κ16) on the other side. Post-treatment was established to render silk fibers insoluble in water. Subsequent AuNP binding was highly selective on the ntagCys eADF4(κ16) side demonstrating the potential of such silk-based systems to realize complex bifunctional structures with spatial resolutions in the nano scale.
| S-EPMC9303884 | biostudies-literature
Project description:The importance of modified peptides and proteins for applications in drug discovery, and for illuminating biological processes at the molecular level, has fueled a demand for efficient methods that facilitate the precise modification of these biomolecules. Herein, we describe the development of a photocatalytic method for the rapid and efficient dimerization and sitespecific functionalization of peptide and protein diselenides. This methodology, dubbed the photocatalytic diselenide contraction (PDC), involves irradiation at 450 nm in the presence of an iridium photocatalyst and a phosphine and results in rapid and clean conversion of diselenides to reductively stable selenoethers. A mechanism for this unprecedented photocatalytic transformation is proposed, which is supported by photoluminescence spectroscopy and density functional theory calculations. The utility of the PDC transformation is highlighted through the dimerization of selenopeptides, and by the generation of two families of protein conjugates via the site-selective modification of calmodulin containing the 21st amino acid selenocysteine, and the C-terminal modification of a ubiquitin diselenide.
2022-10-25 | PXD037525 | Pride
Project description:Protein modifications are often required to study structure and function relationships. Instead of the random labeling of lysine residues, methods have been developed to (sequence) specific label proteins. Next to chemical modifications, tools to integrate new chemical groups for bioorthogonal reactions have been applied. Alternatively, proteins can also be selectively modified by enzymes. Herein we review the methods available for site-specific modification of proteins and their applications for therapeutic antibodies.
| S-EPMC3995230 | biostudies-literature