A5066123877- Monoclonal and Polyclonal Antibodies Research
- Click Chemistry and Applications
- Bioactive Compounds and Antitumor Agents
- Chronic Lymphocytic Leukemia Research
- Cell Adhesion Molecules Research
- Chemical Synthesis and Analysis
- Immunodeficiency and Autoimmune Disorders
- Organic Chemistry Cycloaddition Reactions
- Mast cells and histamine
- Cancer Treatment and Pharmacology
- Quinazolinone synthesis and applications
- Melanoma and MAPK Pathways
- Oxidative Organic Chemistry Reactions
- Glycosylation and Glycoproteins Research
- Protein purification and stability
- Synthesis and Biological Evaluation
- Computational Drug Discovery Methods
- Protein Degradation and Inhibitors
- Machine Learning in Materials Science
- Innovative Microfluidic and Catalytic Techniques Innovation
- Cancer therapeutics and mechanisms
- Peptidase Inhibition and Analysis
- Angiogenesis and VEGF in Cancer
- HER2/EGFR in Cancer Research
- CAR-T cell therapy research
University of Cambridge
2019-2022
Optimizing reaction conditions depends on expert chemistry knowledge and laborious exploration of parameters. To automate this task augment chemical intuition, we here report a computational tool to navigate search spaces. Our approach (LabMate.ML) integrates random sampling 0.03%–0.04% all space as input data with an interpretable, adaptive machine-learning algorithm. LabMate.ML can optimize many real-valued categorical parameters simultaneously, minimal resources time. In nine prospective...
With a resurgence in interest covalent drugs, there is need to identify new moieties capable of cysteine bond formation that are differentiated from commonly employed systems such as acrylamide. Herein, we report on the discovery alkynyl benzoxazine and dihydroquinazoline reaction with cysteine. Their utility alternative electrophilic warheads for chemical biological probes drug molecules demonstrated through site-selective protein modification incorporation into kinase scaffolds. A potent...
Natural products that contain ortho-quinones show great potential as anticancer agents but have been largely discarded from clinical development because their redox-cycling behaviour results in general systemic toxicity. Here we report conjugation of to a carrier, which simultaneously masks underlying redox activity. C-benzylation at quinone carbonyl forms redox-inactive benzyl ketol. Upon specific enzymatic trigger, an acid-promoted, self-immolative C-C bond-cleaving 1,6-elimination...
Antibody-drug conjugates (ADCs) are a class of targeted therapeutics used to selectively kill cancer cells. It is important that they remain intact in the bloodstream and release their payload target cell for maximum efficacy minimum toxicity. The development effective ADCs requires study factors can alter stability these at atomic level. Here, we present general strategy combines synthesis, bioconjugation, linker technology, site-directed mutagenesis, modeling investigate influence site...
Abstract An azanorbornadiene bromovinyl sulfone reagent for cysteine‐selective bioconjugation has been developed. Subsequent reaction with dipyridyl tetrazine leads to bond cleavage and formation of a pyrrole‐linked conjugate. The latter involves ligation the azanorbornadiene‐tagged protein through inverse electron demand Diels–Alder cycloaddition subsequent double retro‐Diels–Alder reactions form stable pyrrole linkage. sequence site‐selective followed by bioorthogonal was efficiently...
Abstract An azanorbornadiene bromovinyl sulfone reagent for cysteine‐selective bioconjugation has been developed. Subsequent reaction with dipyridyl tetrazine leads to bond cleavage and formation of a pyrrole‐linked conjugate. The latter involves ligation the azanorbornadiene‐tagged protein through inverse electron demand Diels–Alder cycloaddition subsequent double retro‐Diels–Alder reactions form stable pyrrole linkage. sequence site‐selective followed by bioorthogonal was efficiently...
Abstract Proteases derived from human pathogens can specifically cleave IgG into F(ab′)2 and Fc fragments. This unique trait suggests a novel opportunity to use these molecules treat auto antibody mediated disease. IdeS, an cleaving enzyme Streptococcus pyogenes has shown clinical proof of concept is approved for before kidney transplant. Due the immunogenic nature proteases, dosing regimen impacted by pre-existing antibodies induction anti-drug after dosing. To mitigate impact immune system...
Abstract Dysregulated humoral immune mechanisms result in immunoglobulin production that is pathogenic and contributes to a wide range of autoimmune diseases transplant rejection. Proteases derived from human pathogens can specifically cleave these immunoglobulins (Ig) potentially eliminate circulating, cell-surface immune-complex Ig classes modulate Ig-mediated autoimmunity inflammation, providing novel opportunity treat antibody-mediated diseases. We describe here the discovery,...
Abstract Proteases derived from human pathogens can specifically cleave IgG into F(ab′)2 and Fc fragments. This unique trait suggests a novel opportunity to use these molecules treat auto antibody mediated disease. IdeS, an cleaving enzyme Streptococcus pyogenes has shown clinical proof of concept is approved for before kidney transplant. Due the immunogenic nature proteases, dosing regimen impacted by pre-existing antibodies induction anti-drug after dosing. To mitigate impact immune system...
Abstract Antibodies play a vital role in the body’s immune defense mechanism. However, pathogenic Ig antibodies are thought to contribute several autoimmune conditions and transplant rejection. Proteases derived from human pathogens can specifically cleave IgG into F(ab’)2 Fc fragments, thus allowing for rapid clearance of IgG. This unique trait suggests novel opportunity use these molecules treat autoantibody mediated diseases. Using our IMPACT platform leveraging machine learning, we have...