Amphiphilic Iodine(III) Reagents for the Lipophilization of Peptides in Water

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...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2021-08, Vol.60 (33), p.17963-17968
Main Authors: Mishra, Abhaya Kumar, Tessier, Romain, Hari, Durga Prasad, Waser, Jerome
Format: Article
Language:English
Subjects:
Alkynes
Amino acids
amphiphilic reagents
Communication
Communications
Cysteine
Homocysteine
Hydroxylamine
hypervalent iodine
Iodine
lipidation
lipopeptide
Lipophilic
Lipophilicity
Peptides
Reagents
Room temperature
Thioesters
Thiols
Ubiquitin
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Summary: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. Amphiphilic hypervalent iodine reagents enable the alkynylation of cysteine residues in peptides with lipophilic groups in water. The reaction proceeds in neutral standard buffers with high efficiency for a broad range of peptides and one protein. The thioalkynes can be converted into cleavable thioesters under acidic conditions.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.202106458