Bis(arylmethyl)-substituted unsymmetrical phosphites for the synthesis of lipidated peptides via Staudinger-phosphite reactions

With this study we introduce new unsymmetrical phosphites to obtain lipidated peptide-conjugates starting from easily accessible azide-modified amino acid or peptide precursors. For this purpose, we investigated which substituents at alkyl phosphites lead to the highest formation of mono-alkylated p...

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Published in:Organic & biomolecular chemistry 2016-01, Vol.14 (31), p.7500-7508
Main Authors: Nischan, N, Kasper, M-A, Mathew, T, Hackenberger, C P R
Format: Article
Language:English
Subjects:
HeLa Cells
Humans
Microscopy, Fluorescence
Molecular Structure
Peptides - chemical synthesis
Peptides - chemistry
Peptides - pharmacokinetics
Phosphites - chemistry
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creator Nischan, N
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description With this study we introduce new unsymmetrical phosphites to obtain lipidated peptide-conjugates starting from easily accessible azide-modified amino acid or peptide precursors. For this purpose, we investigated which substituents at alkyl phosphites lead to the highest formation of mono-alkylated phosphoramidate peptides. We found that phosphites containing one alkyl-chain and two picolyl or benzyl-substituents delivered alkyl phosphoramidate-conjugates in high yields, which also allowed a chemoselective lipidation of an unprotected azido polypeptide. Finally, monolipidated phosphoramidate peptides obtained by the unsymmetrical Staudinger phosphite reaction led to the formation of micelle-like structures and cellular uptake.
doi_str_mv 10.1039/c6ob00843g
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source Royal Society of Chemistry:Jisc Collections:Royal Society of Chemistry Read and Publish 2022-2024 (reading list)
subjects HeLa Cells
Humans
Microscopy, Fluorescence
Molecular Structure
Peptides - chemical synthesis
Peptides - chemistry
Peptides - pharmacokinetics
Phosphites - chemistry
title Bis(arylmethyl)-substituted unsymmetrical phosphites for the synthesis of lipidated peptides via Staudinger-phosphite reactions
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