5-Hydroxy-pyrrolone based building blocks as maleimide alternatives for protein bioconjugation and single-site multi-functionalization

Geyter, Ewout De; Antonatou, Eirini; Kalaitzakis, Dimitris; Smoleń, Sabina; Iyer, Abhishek; Tack, Laure; Ongenae, E; Vassilikogiannakis, Georgios; Madder, Annemieke

doi:10.1039/d0sc05881e

Cited by 11 publications

(12 citation statements)

References 46 publications

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“…89 Related to the 3Br-5MPs are the 5-hydroxy-pyrrolones (5HP2Os) which can be prepared from furan precursors via photooxidation. 90 A noncyclic alternative to the pyrrolones are diamide and amido ester derivatives of maleic acid which react with Cys residues to form either a thiosuccinimide or thiomaleimide. The product can then either undergo hydrolysis to the stable ring-opened maleamic acid moiety or addition of a Lys ε-amino group to form a cyclized protein product with a stable maleimide staple.…”

Section: Reactivity Screeningmentioning

confidence: 99%

Chemical modification of proteins – challenges and trends at the start of the 2020s

2023

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Section: Reactivity Screeningmentioning

confidence: 99%

Chemical modification of proteins – challenges and trends at the start of the 2020s

2023

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“…Maleimides have thus been the object of intense scrutiny and can safely be considered as the mainstay of cysteine conjugation. But despite this dominant position, research towards the development of other thiol-selective reagents based on electron-deficient alkenes (and alkynes) has been quite active-and continues to be [59]. royalsocietypublishing.org/journal/rsos R. Soc.…”

Section: Cysteine Residuesmentioning

confidence: 99%

An overview of chemo- and site-selectivity aspects in the chemical conjugation of proteins

et al. 2022

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The bioconjugation of proteins—that is, the creation of a covalent link between a protein and any other molecule—has been studied for decades, partly because of the numerous applications of protein conjugates, but also due to the technical challenge it represents. Indeed, proteins possess inner physico-chemical properties—they are sensitive and polynucleophilic macromolecules—that make them complex substrates in conjugation reactions. This complexity arises from the mild conditions imposed by their sensitivity but also from selectivity issues, viz the precise control of the conjugation site on the protein. After decades of research, strategies and reagents have been developed to address two aspects of this selectivity: chemoselectivity—harnessing the reacting chemical functionality—and site-selectivity—controlling the reacting amino acid residue—most notably thanks to the participation of synthetic chemistry in this effort. This review offers an overview of these chemical bioconjugation strategies, insisting on those employing native proteins as substrates, and shows that the field is active and exciting, especially for synthetic chemists seeking new challenges.

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“…Labelling a specific (type of) protein or peptide with a dye, radioactive handle or property enhancing moiety has gained substantial interest over the years, since it is a powerful tool to analyze the dynamics of living systems and to synthesize new protein-based biomaterials [ 91 ]. Throughout the years, multiple labelling methods have been reported, for example the azide-alkyne click reaction [ 92 , 93 ], the tetrazine-alkyne inverse electron demand Diels–Alder reaction [ 94 ] and labelling of native moieties in peptides and proteins, such as carbonyl labelling by hydrazines or alkoxyamines [ 95 ], chemoselective labelling of tyrosine [ 96 , 97 ], tryptophane [ 98 ], cysteine [ 99 , 100 ] and lysine [ 101 ]. A detailed overview of such biorthogonal bioconjugation approaches are given by C. S. McKay et al [ 102 ].…”

Section: 1 O 2 In Bioorganic Chemistry Ap...mentioning

confidence: 99%

A Photosensitized Singlet Oxygen (1O2) Toolbox for Bio-Organic Applications: Tailoring 1O2 Generation for DNA and Protein Labelling, Targeting and Biosensing

et al. 2022

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Singlet oxygen (1O2) is the excited state of ground, triplet state, molecular oxygen (O2). Photosensitized 1O2 has been extensively studied as one of the reactive oxygen species (ROS), responsible for damage of cellular components (protein, DNA, lipids). On the other hand, its generation has been exploited in organic synthesis, as well as in photodynamic therapy for the treatment of various forms of cancer. The aim of this review is to highlight the versatility of 1O2, discussing the main bioorganic applications reported over the past decades, which rely on its production. After a brief introduction on the photosensitized production of 1O2, we will describe the main aspects involving the biologically relevant damage that can accompany an uncontrolled, aspecific generation of this ROS. We then discuss in more detail a series of biological applications featuring 1O2 generation, including protein and DNA labelling, cross-linking and biosensing. Finally, we will highlight the methodologies available to tailor 1O2 generation, in order to accomplish the proposed bioorganic transformations while avoiding, at the same time, collateral damage related to an untamed production of this reactive species.

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5-Hydroxy-pyrrolone based building blocks as maleimide alternatives for protein bioconjugation and single-site multi-functionalization

Abstract: Recent expansion in potential uses of protein conjugates has fueled the development of a range of protein modification methods; however, the desirable single-site multi-functionalization of proteins has remained a particularly intransigent challenge.

Cited by 11 publications

References 46 publications

Chemical modification of proteins – challenges and trends at the start of the 2020s

Chemical modification of proteins – challenges and trends at the start of the 2020s

An overview of chemo- and site-selectivity aspects in the chemical conjugation of proteins

A Photosensitized Singlet Oxygen (1O2) Toolbox for Bio-Organic Applications: Tailoring 1O2 Generation for DNA and Protein Labelling, Targeting and Biosensing

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