The Use of 3,6-Pyridazinediones in Organic Synthesis and Chemical Biology

Lee, Maximillian T. W.; Maruani, Antoine; Chudasama, Vijay

doi:10.3184/174751916x14495034614855

Cited by 24 publications

(17 citation statements)

References 49 publications

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“…The DBPD platform has been considerably explored in the generation of ADCs, antibody conjugates, antibody directed photosensitizers, protein‐protein conjugates and targeted nanotherapeutics . A DBPD reagent incorporating a terminal alkyne and cyclooctyne probe was used to accomplish complete rebridging of Trastuzumab (4:1 ratio of PD‐to‐antibody).…”

Section: Other Chemical Approaches For Maleimide‐like Bioconjugationmentioning

confidence: 99%

Bioconjugation with Maleimides: A Useful Tool for Chemical Biology

Ravasco

Faustino

Trindade

et al. 2018

Chemistry A European J

396

347

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Maleimide chemistry stands out in the bioconjugation toolbox by virtue of its synthetic accessibility, excellent reactivity, and practicability. The second-generation of clinically approved antibody-drug conjugates (ADC) and much of the current ADC pipeline in clinical trials contain the maleimide linkage. However, thiosuccinimide linkages are now known to be less robust than once thought, and ergo, are correlated with suboptimal pharmacodynamics, pharmacokinetics, and safety profiles in some ADC constructs. Rational design of novel generations of maleimides and maleimide-type reagents have been reported to address the shortcomings of classical maleimides, allowing for the formation of robust bioconjugate linkages. This review highlights the main strategies for rational reagent design that have allowed irreversible bioconjugations in cysteines, reversible labelling strategies and disulfide re-bridging.

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Section: Other Chemical Approaches For Maleimide‐like Bioconjugationmentioning

confidence: 99%

Bioconjugation with Maleimides: A Useful Tool for Chemical Biology

Ravasco

Faustino

Trindade

et al. 2018

Chemistry A European J

396

347

View full text Add to dashboard Cite

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“…Dibromopyridazinediones (Figure A, V) were reported by Caddick and Chudasama for targeting disulfide bridges in peptides, Fab and antibodies . The synthesis of dibromopyridazinediones can be achieved over three steps by the initial condensation of maleic anhydride with disubstituted hydrazine followed by sequential dibromination/elimination steps with a moderate overall yield (≈60 %) .…”

Section: Disulfide Rebridging Agents: Syntheses Features and Biocmentioning

confidence: 97%

Site‐Selective Disulfide Modification of Proteins: Expanding Diversity beyond the Proteome

Kuan

Wang

Weil

2016

Chemistry A European J

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The synthetic transformation of polypeptides with molecular accuracy holds great promise for providing functional and structural diversity beyond the proteome. Consequently, the last decade has seen an exponential growth of site‐directed chemistry to install additional features into peptides and proteins even inside living cells. The disulfide rebridging strategy has emerged as a powerful tool for site‐selective modifications since most proteins contain disulfide bonds. In this Review, we present the chemical design, advantages and limitations of the disulfide rebridging reagents, while summarizing their relevance for synthetic customization of functional protein bioconjugates, as well as the resultant impact and advancement for biomedical applications.

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“…The Fab of monoclonal antibody Herceptin™ was chosen as the protein platform due to its clinical relevance as an approved therapeutic against HER2+ cancers. 17 The decision to utilise the Fab of a full antibody was driven by a number of factors: (i) the substantial literature inferring antibody fragments/small protein scaffold provide multiple benefits over full antibodies; (ii) Fabs contains a single solvent accessible disulfide bond (distal from the binding site) to ensure homogeneous modification by our previously reported disulfide re-binding technology; 20,22 (iii) Fabs can be readily expressed and/or obtained from native full antibody scaffolds via simple enzymatic digestion procedures. 17 This part of the study began with the formation of Herceptin™ Fab from full antibody Herceptin™ by enzymatic digestion ( pepsin followed by papain, further details provided in the ESI †).…”

Section: Functionalisation Of Plga-n 3 Microparticles With Fab Antibomentioning

confidence: 99%