Cell therapies such as CAR-T have demonstrated significant clinical successes, driving the investigation of immune cell surface engineering using natural and synthetic materials to enhance their therapeutic performance. However, many of these materials do not fully replicate the dynamic nature of the extracellular matrix (ECM). This study presents a cell surface engineering strategy that utilizes phase-separated peptide coacervates to decorate the surface of immune cells.
View Article and Find Full Text PDFSerine-arginine (SR) proteins are splicing factors that play essential roles in both constitutive and alternative pre-mRNA splicing. Phosphorylation of their C-terminal RS domains by SR protein kinases (SRPKs) regulates their localization and diverse cellular activities. Dysregulation of phosphorylation has been implicated in many human diseases, including cancers.
View Article and Find Full Text PDFTargeted immunotherapies capitalize on the exceptional binding capabilities of antibodies to stimulate a host response that effectuates long-lived tumor destruction. One example is the conjugation of immunoglobulins (IgGs) to immune effector cells, which equips the cells with the ability to recognize and accurately kill malignant cells through a process called antibody-dependent cellular cytotoxicity (ADCC). In this study, a chemoenzymatic reaction is developed that specifically functionalizes a single tyrosine (Tyr, Y) residue, Y296, in the Fc domain of therapeutic IgGs.
View Article and Find Full Text PDFMethods Mol Biol
September 2023
Proximal crosslinking refers to the site-specific conjugation reaction between a synthetic ligand with a bioorthogonal reactive group incorporated at a particular site and a protein of interest (POI). The binding interaction positions a reactive group of a native amino acid of the POI to the proximity of the reactive group in the ligand. The covalent conjugation increases the molecular weight of the POI, shows an upshift in the polyacrylamide gel, and gives a fluorescent band if the ligand is fluorescently labeled.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
October 2023
Cellular membranes, including the plasma and endosome membranes, are barriers to outside proteins. Various vehicles have been devised to deliver proteins across the plasma membrane, but in many cases, the payload gets trapped in the endosome. Here we designed a photo-responsive phase-separating fluorescent molecule (PPFM) with a molecular weight of 666.
View Article and Find Full Text PDFA key step in enteropathogenic Escherichia coli (EPEC) infection of intestinal cells involves a Tir-induced actin reorganization. Nck mediates this event by binding with WIP through its second SH3 domain (Nck-SH3.2).
View Article and Find Full Text PDFHere we report a method to synthesize C-terminally modified peptides on resin. A four-component Ugi reaction of isocyanide resin, an Fmoc-protected amino acid, an amine, and a 6-nitroveratrylaldehyde gives C-terminal photocaged peptide amides, which can be photolyzed to generate C-terminal peptide amides. Changing the amine component in the Ugi reaction gives peptides with different C-terminal modifications including substituted anilides, alkyne, and azide.
View Article and Find Full Text PDFIntroduction: Proton pump inhibitors (PPIs) are widely prescribed and generally well tolerated but can rarely cause severe allergic reactions, such as drug rash with eosinophilia and systemic symptoms (DRESS). We report a case of DRESS and renal injury induced by PPIs, and describe the therapeutic process.
Patient Concerns: The patient was a 66-year-old female who complained of fever, pruritus, desquamation, erythema multiforme, and anuria caused by omeprazole taken for 2 weeks to treat abdominal distention.
A phosphine-catalyzed reaction between o-hydroxyaryl azomethine ylides and MBH carbonates provides access to highly functionalized γ-aminobutyric acid derivatives in moderate to good yields. Mechanistically, the reaction involves a phosphine-catalyzed tandem S2'/2-aza-Cope rearrangement/intramolecular addition process.
View Article and Find Full Text PDFIn this work, we present a strategy for the stereoselective synthesis of functionalized benzooxazepino[5,4- a]isoindolone derivatives via a CsCO-catalyzed domino β-addition and γ-aldol reaction of 2-(2-hydroxyphenyl)isoindoline-1,3-dione derivatives with allenoates, which offers an avenue for a combination of the structural unity between benzooxazepine and isoindolone motifs in synthetically useful yields with high stereoselectivities under mild conditions. Remarkably, it is the first example of highly stereoselective CsCO-catalyzed formal [5 + 2] annulation of 2-(2-hydroxyphenyl)isoindoline-1,3-dione with allenoates.
View Article and Find Full Text PDFA highly regio- and stereoselective synthesis of β-haloalkenyl sulfides using commercially available ketones and sulfonyl hydrazides as starting materials has been developed. This protocol obviates the need for alkynes and traditional sulfenylating agents and therefore opens up a new door to construct β-iodoalkenyl sulfides in a highly simple manner. This study reveals that ketones could be used as vinyl iodide precursors in organic synthesis.
View Article and Find Full Text PDFIn this work, we present a new strategy for the chemo-, regio-, and stereoselective synthesis of functionalized pyrrolidine derivatives via a hydroxy-assisted phosphine-catalyzed reaction of allenoates or substituted allenoates with o-hydroxyaryl azomethine ylides that offers a wide variety of 4-methylenepyrrolidine derivatives in synthetically useful yields with high stereoselctivities under mild conditions. Remarkably, it is the first example of highly regio- and stereoselective phosphine-catalyzed [3 + 2] cycloaddition of allenoates with o-hydroxyaryl azomethine ylides.
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