Advancing Biomarker Detection with Peptide-Integrated Fluorescent Probes.

Over-expressed biomarkers such as proteins, enzymes, and so forth are directly linked to various diseases. Hence, the timely detection of the biomarkers using the optical probes is a useful technique for the disease detection or early-stage prediction of a disease. Although, one of the major hurdles for this technique is the biocompatibility of the probe.

One-Pot Synthesis of Vinylogous Cyano Aminoaryls (VinCAs) as Benzenic Fluorophores: Tailoring Diverse Emission Colors for White Light Emitting Materials and Cell Imaging.

Donor-acceptor-based organic small molecules with an electronic push-pull effect can demonstrate intramolecular charge transfer to show interesting photoluminescence properties. This is an essential criterion for designing fluorogenic probes for cell imaging studies and the development of organic light-emitting diodes. Now, to design such optical materials sometimes it is necessary to tune the band gap by controlling the energies of the highest occupied molecular orbital and lowest unoccupied molecular orbital.

Nontoxic Aggregation-Induced Emissive Luminogen for the Detection of Amyloid Fibrils and Cellular Protein Aggregates.

Protein misfolding and aggregation resulting in amyloid formation is directly linked to various diseases. Hence, there is keen interest in developing probes for the selective detection of such misfolded aggregated proteins. In this paper, we have shown the use of a nontoxic aggregation-induced emissive luminogen (AIEgen), BIDCPV, for the selective detection of insulin amyloid fibrils and their various stages of formation.

A convenient route to a vinylogous dicyano aryl based AIEgen with switchable mechanochromic luminescence properties.

Molecules with solid state luminescence and mechanochromic luminescence properties have attracted immense interest owing to their potential application in the areas of organic field-effect transistors (OFETs), organic light-emitting diodes (OLEDs), optoelectronic devices, fluorescence switches, mechano-sensors and data storage. Herein we report a convenient two step synthetic protocol to obtain a couple of luminescent molecules. Using these, a comparative study has been performed to showcase the importance of the weak π⋯π interactions to observe the aggregation induced emission (AIE) and solid-state mechanochromic luminescence.

Polymer with Competing Depolymerization Pathways: Chain Unzipping versus Chain Scission.

Interest in triggered depolymerization is growing, driven by needs in sustainable plastics, self-healing materials, controlled release, and sensory amplification. For many triggered depolymerization reactions, the rate-limiting step does not directly involve the stimulus, and therefore, depolymerization kinetics exhibit only weak or no correlation to the concentration and reactivity of the stimulus. However, for many applications, a direct relationship between the stimulus and the depolymerization kinetics is desired.

Labeling Proteins at Site-Specifically Incorporated 5-Hydroxytryptophan Residues Using a Chemoselective Rapid Azo-Coupling Reaction.

Chemoselective protein labeling is a valuable tool in the arsenal of modern chemical biology. The unnatural amino acid mutagenesis technology provides a powerful way to site-specifically introduce nonnatural chemical functionalities into recombinant proteins, which can be subsequently functionalized in a chemoselective manner. Even though several strategies currently exist to selectively label recombinant proteins in this manner, there is considerable interest for the development of additional chemoselective reactions that are fast, catalyst-free, use readily available reagents, and are compatible with existing conjugation chemistries.

Mutually Orthogonal Nonsense-Suppression Systems and Conjugation Chemistries for Precise Protein Labeling at up to Three Distinct Sites.

Site-specific incorporation of multiple distinct noncanonical amino acids (ncAAs) into a protein is an emerging technology with tremendous potential. It relies on mutually orthogonal engineered aminoacyl-tRNA synthetase/tRNA pairs that suppress different nonsense/frameshift codons. So far, up to two distinct ncAAs have been incorporated into proteins expressed in E.

A "Quenchergenic" Chemoselective Protein Labeling Strategy.

Dynamic changes in protein structure can be monitored by using a fluorescent probe and a dark quencher. This approach is contingent upon the ability to precisely introduce a fluorophore/quencher pair into two specific sites of a protein of interest. Despite recent advances, there is continued demand for new and convenient approaches to site-selectively label proteins with such optical probes.

An Oxidative Bioconjugation Strategy Targeted to a Genetically Encoded 5-Hydroxytryptophan.

Approaches that enable the chemoselective, covalent modification of proteins in a site-specific manner have emerged as a powerful technology for a wide range of applications. The electron-rich unnatural amino acid 5-hydroxytryptophan was recently genetically encoded in both Escherichia coli and eukaryotes, thereby allowing its site-specific incorporation into virtually any recombinant protein. Herein, we report the chemoselective conjugation of various aromatic amines to full-length proteins under mild, oxidative conditions that target this site-specifically incorporated 5-hydroxytryptophan residue.

Defining the current scope and limitations of dual noncanonical amino acid mutagenesis in mammalian cells.

The ability to site-specifically incorporate two distinct noncanonical amino acids (ncAAs) into the proteome of a mammalian cell with high fidelity and efficiency will have many enabling applications. It would require the use of two different engineered aminoacyl-tRNA synthetase (aaRS)/tRNA pairs, each suppressing a distinct nonsense codon, and which cross-react neither with each other, nor with their counterparts from the host cell. Three different aaRS/tRNA pairs have been developed so far to expand the genetic code of mammalian cells, which can be potentially combined in three unique ways to drive site-specific incorporation of two distinct ncAAs.

Laser desorption ionization mass spectrometry: Recent progress in matrix-free and label-assisted techniques.

The MALDI-based mass spectrometry, over the last three decades, has become an important analytical tool. It is a gentle ionization technique, usually applicable to detect and characterize analytes with high molecular weights like proteins and other macromolecules. The earlier difficulty of detection of analytes with low molecular weights like small organic molecules and metal ion complexes with this technique arose due to the cluster of peaks in the low molecular weight region generated from the matrix.

A Chemoselective Rapid Azo-Coupling Reaction (CRACR) for Unclickable Bioconjugation.

Chemoselective modification of complex biomolecules has become a cornerstone of chemical biology. Despite the exciting developments of the past two decades, the demand for new chemoselective reactions with unique abilities, and those compatible with existing chemistries for concurrent multisite-directed labeling, remains high. Here we show that 5-hydroxyindoles exhibit remarkably high reactivity toward aromatic diazonium ions and this reaction can be used to chemoselectively label proteins.

An orthogonalized platform for genetic code expansion in both bacteria and eukaryotes.

In this study, we demonstrate the feasibility of expanding the genetic code of Escherichia coli using its own tryptophanyl-tRNA synthetase and tRNA (TrpRS-tRNA) pair. This was made possible by first functionally replacing this endogenous pair with an E. coli-optimized counterpart from Saccharomyces cerevisiae, and then reintroducing the liberated E.

A Unique Genetically Encoded FRET Pair in Mammalian Cells.

Förster resonance energy transfer (FRET) between two suitable fluorophores is a powerful tool to monitor dynamic changes in protein structure in vitro and in vivo. The ability to genetically encode a FRET pair represents a convenient "labeling-free" strategy to incorporate them into target protein(s). Currently, the only genetically encoded FRET pairs available for use in mammalian cells use fluorescent proteins.

Shifting the Reactivity of Bis-propargyl Ethers from Garratt-Braverman Cyclization Mode to 1,5-H Shift Pathway To Yield 3,4-Disubstituted Furans: A Combined Experimental and Computational Study.

Aryl or vinyl substituted bis-propargyl ethers upon base treatment generally form phthalans via the Garratt-Braverman (GB) cyclization pathway. In a major departure from this usual route, several aryl/vinyl bis-propargyl ethers with one of the acetylenic arms ending up with 2-tetrahydropyranyloxy methyl or ethoxy methyl have been shown to follow the alternative intramolecular 1,5-H shift pathway upon base treatment. The reaction has led to the formation of synthetically as well as biologically important 3,4-disubstituted furan derivatives in good yields.

1,3,5-Trisubstituted benzenes as fluorescent photoaffinity probes for human carbonic anhydrase II capture.

The synthesis of small molecule based 1,3,5-trisubstituted benzenes for photo-mediated capture of human carbonic anhydrase II with visualisation by fluorescence is described.