Abstract
We report the functionalization of cysteine residues with lipophilic alkynes bearing a silyl group or an alkyl chain using amphiphilic ethynylbenziodoxolone reagents (EBXs). The reactions were carried out in buffer (pH 6 to 9), without organic co‐solvent or removal of oxygen, either at 37 °C or room temperature. The transformation led to a significant increase of peptide lipophilicity and worked for aromatic thiols, homocysteine, cysteine, and peptides containing 4 to 18 amino acids. His6‐Cys‐Ubiquitin was also alkynylated under physiological conditions. Under acidic conditions, the thioalkynes were converted into thioesters, which could be cleaved in the presence of hydroxylamine.
Highlights
We report the functionalization of cysteine residues with lipophilic alkynes bearing a silyl group or an alkyl chain using amphiphilic ethynylbenziodoxolone reagents (EBXs)
Many reported lipidation processes use highly reactive reagents together with organic co-solvents, due to the low solubility of the lipophilic reagents, which can be an issue in presence of sensitive biomolecules
There are only few reagents for cysteine functionalization that are fully water-soluble,[14] and only reagent E was reported for the specific case of lipidation, based on the formation of labile disulfide bridges.[14a]
Summary
The authors declare no conflict of interest. Keywords: amphiphilic reagents · hypervalent iodine · lipidation · lipopeptide · ubiquitin [1] C. [7] Selective examples of amphiphilic peptides in materials sciences: a) J. [9] Selected examples and reviews: a) E. F. Kirsch, Synthesis 2015, 47, 1937 – 1943; e) M. Angewandte Chemie International Edition published by Wiley-VCH GmbH www.angewandte.org 17967. [20] According to ICP-MS, potassium (K) was in major part exchanged with sodium (Na) during the synthesis; see the Supporting Information. Angewandte Chemie International Edition published by Wiley-VCH GmbH Angew.
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