Synthesis of C-terminal glycopeptides from resin-bound glycosyl azides via a modified staudinger reaction

Malkinson, John P., Falconer, Robert A. and Toth, Istvan (2000) Synthesis of C-terminal glycopeptides from resin-bound glycosyl azides via a modified staudinger reaction. Journal of Organic Chemistry, 65 17: 5249-5252. doi:10.1021/jo000381z


Author Malkinson, John P.
Falconer, Robert A.
Toth, Istvan
Title Synthesis of C-terminal glycopeptides from resin-bound glycosyl azides via a modified staudinger reaction
Journal name Journal of Organic Chemistry   Check publisher's open access policy
ISSN 0022-3263
Publication date 2000
Sub-type Article (original research)
DOI 10.1021/jo000381z
Volume 65
Issue 17
Start page 5249
End page 5252
Total pages 4
Place of publication Washington D.C., USA
Publisher American Chemical Society
Collection year 2000
Language eng
Subject C1
320501 Pharmaceutical Sciences and Pharmacy
670400 Human Pharmaceutical Products
Abstract The solid-phase synthesis of glycopeptides containing the sugar at the C-terminus is reported. The method is demonstrated on a model, the endogenous antinociceptive peptide Leu-enkephalin. 2,3,4- Tri-O-acetyl-1-azido-1-deoxy-beta-D-glucopyranuronic acid was synthesized and immobilized onto a variety of derivatized resins. Conjugation of the first amino acid was accomplished by reaction of the resin-bound glycosyl azide with an activated amino acid, in one step, via a modified Staudinger reaction. Standard solid-phase peptide synthesis then resulted in the desired amide-linked glycopeptide. Reaction conditions and reagents for the glycosylation were varied to optimize the yield and purity of the product. The optimum conditions were found to be the use of a 4-fold molar excess of activated amino acid and 3-fold excess of tri-n-butylphosphine in tetrahydrofuran. This methodology is generally applicable to most peptide sequences and is compatible with both Bocand Fmoc- synthetic strategies on a variety of resins.
Keyword Chemistry, Organic
Carbohydrate-modified Enkephalins
Solid-phase Synthesis
Derivatives
Asparagine
Brain
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Pharmacy Publications
 
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Created: Tue, 10 Jun 2008, 12:50:43 EST