A5005043054- Click Chemistry and Applications
- Chemical Synthesis and Analysis
- Catalytic Cross-Coupling Reactions
- Synthetic Organic Chemistry Methods
- Radiopharmaceutical Chemistry and Applications
- Advanced biosensing and bioanalysis techniques
- Crystallization and Solubility Studies
- Boron Compounds in Chemistry
- X-ray Diffraction in Crystallography
- Biotin and Related Studies
- Monoclonal and Polyclonal Antibodies Research
- Asymmetric Synthesis and Catalysis
- Chemical Synthesis and Reactions
- Cyclopropane Reaction Mechanisms
- RNA Interference and Gene Delivery
- Synthesis and Catalytic Reactions
- Microbial Natural Products and Biosynthesis
- Orthopedic Infections and Treatments
- HER2/EGFR in Cancer Research
- Chemical synthesis and alkaloids
- CAR-T cell therapy research
- Catalytic C–H Functionalization Methods
- Advanced Synthetic Organic Chemistry
- Sulfur-Based Synthesis Techniques
- Carbohydrate Chemistry and Synthesis
Massachusetts Institute of Technology
2020-2024
Baylor University
2016-2017
California State University, Northridge
2010-2011
Few chemical methods exist for the covalent conjugation of two proteins. We report preparation site-specific protein-protein conjugates that arise from sequential cross-coupling cysteine residues on different The method involves synthesis stable palladium-protein oxidative addition complexes (Pd-protein OACs), a process converts nucleophilic into an electrophilic S-aryl-Pd-X unit by taking advantage intramolecular strategy. This is demonstrated proteins up to 83 kDa in size and can be...
Carboranes represent a class of compounds with increasing therapeutic potential. However, few general approaches to readily embed carboranes into small molecules, peptides, and proteins are available. We report strategy based on palladium-mediated C–X (X = C, S, N) bond formation for the installation carborane-containing moieties onto molecules peptides. demonstrate ability Pd-based reagents appropriate ligands overcome high hydrophobicity carborane group enable chemoselective conjugation...
The utility of antibody therapeutics is hampered by potential cross-reactivity with healthy tissue. Over the past decade, significant advances have been made in design activatable antibodies, which increase, or create altogether, therapeutic window a parent antibody. Of these, prodrugs (pro-antibodies) are masked antibodies that advanced most for use. They designed to reveal active, only when encountering proteases upregulated microenvironment targeted disease tissue, thereby minimizing...
Organometallic reagents enable practical strategies for bioconjugation. Innovations in the design of water-soluble ligands and enhancement reaction rates have allowed chemoselective cross-coupling reactions peptides proteins to be carried out water. There are currently no organometallic-based methods oligonucleotide bioconjugation other biomolecules. Here we report bifunctional palladium(II)-oxidative addition complexes (OACs) as high-yielding reactions. These OACs react chemoselectively...
Described herein are syntheses of the naturally occurring polyketides (-)-tetrapetalones A and C their respective enantiomers. The employed strategy involves initial assembly a masked N-aryl tetramic acid which is advanced via highly selective conjugate addition/intramolecular Friedel-Crafts acylation sequence to deliver key azepine intermediate. Application recently developed C-H activation chemistry subsequent Heck cyclization delivers aglycone framework in an overall 12 steps. Resolution...
Palladium oxidative addition complexes (OACs) are traditionally accessed by treating an aryl halide-containing substrate with a palladium(0) source. Here, new strategy to selectively prepare stable OACs from amino groups on native proteins is presented. The approach relies amine-selective acylation reaction that occurs without modification of preformed palladium(II)-aryl group. Once transferred onto protein substrate, the group facilitates conjugation undergoing second, cysteine-containing...
Catalyst transfer polymerization (CTP) is widely applied to the synthesis of well-defined π-conjugated polymers. Unlike other reactions that can be performed in water (e.g., controlled radical polymerizations and ring-opening polymerizations), CTP has yet adapted for modification biopolymers. Here, we report use protein-palladium oxidative addition complexes (OACs) enable catalyst furnish protein-polyarene conjugates. These occur with electron-deficient monomers aqueous buffers open air at...
The synthesis of palladium oxidative addition complexes derived from unprotected peptides is described. Incorporation 4-halophenylalanine into a peptide during solid phase allows for subsequent at this position upon treatment with precursor and suitable ligand. resulting palladium-peptide are solid, storable, water-soluble, easily purified via high-performance liquid chromatography. These react thiols in aqueous buffer, offering an efficient method bioconjugation. Using strategy, can be...
Amphiphilic ligands are valued for their ability to facilitate organometallic reactions in the presence of water. The regioselective sulfonation a series commercially available biaryl monophosphines generate amphiphilic is presented. In this one-step protocol, temperature and addition fuming sulfuric acid were carefully controlled arrive at sulfonated monophosphine high yields with >95% regioselectivity without need chromatographic purification.
Abstract Organometallic reagents enable practical strategies for bioconjugation. Innovations in the design of water‐soluble ligands and enhancement reaction rates have allowed chemoselective cross‐coupling reactions peptides proteins to be carried out water. There are currently no organometallic‐based methods oligonucleotide bioconjugation other biomolecules. Here we report bifunctional palladium(II)‐oxidative addition complexes (OACs) as high‐yielding reactions. These OACs react...
Amphiphilic ligands are valued for their ability to facilitate organometallic reactions in the presence of water. The regioselective sulfonation a series commercially available biaryl monophosphines generate amphiphilic is presented. In this one-step protocol, temperature and addition fuming sulfuric acid were carefully controlled arrive at sulfonated monophosphine high yields with >95% regioselectivity without need chromatographic purification.
The utility of antibody therapeutics is hampered by potential cross-reactivity with healthy tissue. Over the past decade, significant advances have been made in design activatable antibodies which increase, or create altogether, therapeutic window a parent antibody. Of these, prodrugs (pro-antibodies) are masked that advanced most for use. They designed to reveal active, only when encountering proteases upregulated microenvironment targeted disease tissue, thereby minimizing off-target...
Abstract The synthetic utility of indium reagents derived from substrates such as (I) is demonstrated for the title reactions.
<div> <p>Amphiphilic ligands are valued for their ability to facilitate organometallic reactions in the presence of water. The regioselective sulfonation a series commercially available biaryl monophosphines generate amphiphilic is presented. In this one-step protocol, temperature and addition fuming sulfuric acid were carefully controlled arrive at sulfonated monophosphine high yields with >95% regioselectivity without need chromatographic purification.</p> </div>