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...

Full description

Saved in:
Bibliographic Details
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
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1477-0520
1477-0539
DOI:10.1039/c6ob00843g