Bringing enzymes to the proximity party

Tender, Gabrielle S.; Bertozzi, Carolyn R.

doi:10.1039/d3cb00084b

Cited by 8 publications

(2 citation statements)

References 110 publications

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“…The tethering CK2α to the surface provides another example of how surface-tethering of enzymes increases their efficacy as has been shown with ligases, 34,35 proteases, 36 and sialidases, 37 among other enzymes. 49 This enzyme tethering strategy was very useful to investigate and enhance the substrate scope of this kinase. We identified several tumor-associated antigens that are surface substrates of CK2α, including CD44, Galectin-3, and CD109.…”

Section: Discussionmentioning

confidence: 99%

Chemoproteomics reveals immunogenic and tumor-associated cell surface substrates of ectokinase CK2α

Delaveris,

Kong,

Glasgow

et al. 2024

Preprint

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New epitopes for immune recognition provide the basis of anticancer immunity. Due to the high concentration of extracellular adenosine triphosphate in the tumor microenvironment, we hypothesized that extracellular kinases (ectokinases) could have dysregulated activity and introduce aberrant phosphorylation sites on cell surface proteins. We engineered a cell-tethered version of the extracellular kinase CK2α, demonstrated it was active on cells under tumor-relevant conditions, and profiled its substrate scope using a chemoproteomic workflow. We then demonstrated that mice developed polyreactive antisera in response to syngeneic tumor cells that had been subjected to surface hyperphosphorylation with CK2α. Interestingly, these mice developed B cell and CD4+ T cell responses in response to these antigens but failed to develop a CD8+ T cell response. This work provides a workflow for probing the extracellular phosphoproteome and demonstrates that extracellular phosphoproteins are immunogenic even in a syngeneic system.

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Section: Discussionmentioning

confidence: 99%

Chemoproteomics reveals immunogenic and tumor-associated cell surface substrates of ectokinase CK2α

Delaveris,

Kong,

Glasgow

et al. 2024

Preprint

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“…The concept of using an antibody or nonantibody binding scaffold to direct a payload to a specific target can be mixed and matched. For example, the payload has been changed to other functional molecules, e.g., oligonucleotides, enzymes (proteases) for targeted degradation of cancer-associated mucins , or the conversion of prodrugs, and radioisotopes which enable diagnostic and/or closely related therapeutic applications (Figure ). Also the assembly of nanobodies into polyvalent multimers increasing the accessible range of nanobody assembly topologies was performed using ncAA 250 .…”

Section: Applications Of Noncanonical Amino Acidsmentioning

confidence: 99%

Evolution of Pyrrolysyl-tRNA Synthetase: From Methanogenesis to Genetic Code Expansion

Koch,

Budisa

2024

Chem. Rev.

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Over 20 years ago, the pyrrolysine encoding translation system was discovered in specific archaea. Our Review provides an overview of how the once obscure pyrrolysyl-tRNA synthetase (PylRS) tRNA pair, originally responsible for accurately translating enzymes crucial in methanogenic metabolic pathways, laid the foundation for the burgeoning field of genetic code expansion. Our primary focus is the discussion of how to successfully engineer the PylRS to recognize new substrates and exhibit higher in vivo activity. We have compiled a comprehensive list of ncAAs incorporable with the PylRS system. Additionally, we also summarize recent successful applications of the PylRS system in creating innovative therapeutic solutions, such as new antibody−drug conjugates, advancements in vaccine modalities, and the potential production of new antimicrobials. CONTENTS 6.3.3. Antimicrobials 6.3.4. Premature Termination Codon 6.4. Other Biotechnological Applications 7. Expanding the Scope of OTS by Reassigning Sense Codons and Designing Codon Sizes 7.1. Opportunities and Obstacles of Extending the Codon Size for GCE 7.2. Breaking the Degeneracy of the Triplet Code−Sense Codon Reassignment for OTS 8.

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Smart Materials for Biocatalysis Regulation through Thermoresponsive Polymers

de Barros,

Theisen,

Durigon

et al. 2024

ChemCatChem

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Temperature‐responsive biocatalytic hybrid materials offer several advantages, such as improved stability, enhanced catalytic efficiency, and biocatalysts longer lifespan. Combining enzymes with thermoresponsive polymers in a strategically manner allows a smarter modulation of enzyme activity in response to temperature changes. Thermoresponsive materials can act as protective barriers for enzymes or enable controlled exposure and release depending on temperature variations, expanding enzyme applications in diverse environments. This review aims to comprehensively present the design strategies for enzyme‐polymer hybrid materials with thermoresponsive properties, and to address the advantages, applications, and challenges involved for a rational control of biocatalytic systems. The study emphasizes the importance of creating stimuli‐responsive biocatalytic hybrid materials for diverse applications, ranging from controlled drug delivery to industrial catalysis. Furthermore, we outline key research opportunities and future perspectives for studies within this scope.

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Bringing enzymes to the proximity party

Abstract: Targeted enzymes can drive cell type-selective reactions that are not yet possible with other therapeutic approaches.

Cited by 8 publications

References 110 publications

Chemoproteomics reveals immunogenic and tumor-associated cell surface substrates of ectokinase CK2α

Chemoproteomics reveals immunogenic and tumor-associated cell surface substrates of ectokinase CK2α

Evolution of Pyrrolysyl-tRNA Synthetase: From Methanogenesis to Genetic Code Expansion

Smart Materials for Biocatalysis Regulation through Thermoresponsive Polymers

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