Exploiting furan's versatile reactivity in reversible and irreversible orthogonal peptide labeling

Hoogewijs, Kurt; Buyst, Dieter; Winne, Johan M.; Martins, José; Madder, Annemieke

doi:10.1039/c3cc40588e

Cited by 33 publications

(25 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This enables spatiotemporal control of crosslinking and offers enhanced penetration depths in biological samples. A further benefit of furan incorporation into biomolecules is its use in a variety of labelling approaches7 based on Diels–Alder cycloadditions, aromatic substitutions7c and oxidation/reductive amination 7d…”

Section: Methodsmentioning

confidence: 99%

Seaweed‐Derived Heteroatom‐Doped Highly Porous Carbon as an Electrocatalyst for the Oxygen Reduction Reaction

et al. 2014

View full text Add to dashboard Cite

We report the template-free pyrolysis of easily available natural seaweed, Undaria pinnatifida, as a single precursor, which results in "seaweed carbon" (SCup). Interestingly, thus-obtained SCup not only contains heteroatoms such as nitrogen and sulfur in its framework, but it also possesses a well-developed porous structure with high surface area. The heteroatoms in SCup originate from the nitrogen- and sulfur-containing ingredients in seaweed, whereas the porosity is created by removal of salts inherently present in the seaweed. These essential and fundamental properties make seaweed a prime choice as a precursor for heteroatom-containing highly porous carbon as a metal-free efficient electrocatalyst. As-synthesized SCup showed excellent electrocatalytic activity in the oxygen reduction reaction (ORR) in alkaline medium, which can be addressed in terms of the presence of the nitrogen and sulfur heteroatoms, the well-developed porosity, and the electrical conductivity in the carbon framework. The pyrolysis temperature was a key controlling parameter that determined the trade-off between heteroatom doping, surface properties, and electrical conductivity. In particular, SCup prepared at 1000 °C showed the best ORR performance. Additionally, SCup exhibited enhanced durability and methanol tolerance relative to the state of the art commercial Pt catalyst, which demonstrates that SCup is a promising alternative to costly Pt-based catalysts for the ORR.

show abstract

Section: Methodsmentioning

confidence: 99%

Seaweed‐Derived Heteroatom‐Doped Highly Porous Carbon as an Electrocatalyst for the Oxygen Reduction Reaction

et al. 2014

View full text Add to dashboard Cite

show abstract

“…It is a small aromatic heterocycle, relatively stable featuring orthogonal Diels-Alder reactivity, which was previously exploited in cross-link and labeling reactions. 44,45 However it has been classified by the international agency for research on cancer as a class 2B compound, or a possible human carcinogen 46 and by the European food safety authority as genotoxic and carcinogenic. 47 The Peterson group thoroughly studied the toxicity of furan, when taken up by humans through its presence in heat processed food [48][49][50][51][52] and found that it is oxidized in the body by cytochrome P450 enzymes to the very reactive butenedial that quickly reacts with surrounding nucleophiles such as the amino acid side chains (thiols of cysteines or amines of lysines) of proteins or the exocyclic amines of the nucleobases 50,53,54 (Fig.…”

Section: A Maddermentioning

confidence: 99%

Furan oxidation based cross-linking: a new approach for the study and targeting of nucleic acid and protein interactions

et al. 2016

View full text Add to dashboard Cite

Furan mediated nucleic acid cross-linking, initially developed for DNA interstrand duplex cross-linking, has matured into a versatile tool for the study of protein and nucleic acid interactions, ready to face its applications. The methodology was initially developed for easy and clean chemical generation of DNA interstrand cross-linked duplexes, but has been further expanded for use with other probes, targets and triggers, now allowing mild biologically significant cross-linking with potential therapeutic benefit. It was shown that the methodology could be repurposed for RNA interstrand cross-linking, which is very relevant in today's antisense approaches or miRNA target identification endeavors. This further illustrates the furan oxidation method's generality and mildness, especially when using red light for oxidation. A complementary antigene approach has been explored through duplex targeting with furan modified triplex forming oligonucleotides (TFOs) and DNA binding proteins. Also targeting of peptides and proteins by furan-modified DNA and peptides has been explored. Thorough methodology examination exploring variable reaction conditions in combination with a series of different furan-modified building blocks and application of different activation signals resulted in a detailed understanding of the mechanisms involved and factors influencing the yield and selectivity of the reaction. In order to draw the bigger picture of the scope and limitations of furan-oxidation cross-linking, we here provide a unique side by side comparison and discussion of our published data, supplemented with unpublished results, providing a clear performance report of the currently established furan toolbox and its application potential in various biomacromolecular complexes.

show abstract

“…In addition to the CuAAC, the bioorthogonal toolbox encompasses several other functional groups for the convenient conjugation of biomolecules. , One of these is the photoinducible furyl group, which undergoes ring-opening under UV irradiation, forming a highly reactive unsaturated dicarbonyl moiety . By subsequent addition of nucleophiles, this mechanism has been used for the labeling of nucleotides and peptides. − Consequently, Furala was chosen as an additional bioorthogonal substrate. Despite its aromaticity, none of the MC-YR producing strains accepted it as a substrate in position 2.…”

Section: Results and Discussionmentioning

confidence: 99%

Precursor-Directed Biosynthesis and Fluorescence Labeling of Clickable Microcystins

et al. 2020

View full text Add to dashboard Cite

Microcystins, cyclic nonribosomal heptapeptides, are the most well-known cyanobacterial toxins. They are exceptionally well studied, but open questions remain concerning their physiological role for the producing microorganism or their suitability as lead compounds for anticancer drug development. One means to study specialized metabolites in more detail is the introduction of functional groups that make a compound amenable for bioorthogonal, so-called click reactions. Although it was reported that microcystins cannot be derivatized by precursordirected biosynthesis, we successfully used this approach to prepare clickable microcystins. Supplementing different azide-or terminal alkyne containing amino acid analogues into the cultivation medium of microcystin-producing cyanobacteria strains, we found that these strains differ strongly in their substrate acceptance. Exploiting this flexibility, we generated more than 40 different clickable microcystins. We conjugated one of these derivatives with a fluorogenic dye and showed that neither incorporation of the unnatural amino acid analogue nor attachment of the fluorescent label significantly affects the cytotoxicity against cell lines expressing the human organic anion transporting polypeptides 1B1 or 1B3. Using time-lapse microscopy, we observed that the fluorescent microcystin is rapidly taken up into eukaryotic cells expressing these transporters.

show abstract

Exploiting furan's versatile reactivity in reversible and irreversible orthogonal peptide labeling

Cited by 33 publications

References 34 publications

Seaweed‐Derived Heteroatom‐Doped Highly Porous Carbon as an Electrocatalyst for the Oxygen Reduction Reaction

Seaweed‐Derived Heteroatom‐Doped Highly Porous Carbon as an Electrocatalyst for the Oxygen Reduction Reaction

Furan oxidation based cross-linking: a new approach for the study and targeting of nucleic acid and protein interactions

Precursor-Directed Biosynthesis and Fluorescence Labeling of Clickable Microcystins

Contact Info

Product

Resources

About