Research aimed at understanding the specific role of glycosylation patterns in protein function would greatly benefit from additional approaches allowing direct access to homogeneous glycoproteins. Herein the development and application of an efficient approach for the synthesis of complex homogenously glycosylated peptides based on a multifunctional photocleavable auxiliary is described. The presence of a PEG polymer within the auxiliary enables sequential enzymatic glycosylation and straightforward isolation in excellent yields. The auxiliary-modified peptides can be directly used in native chemical ligations with peptide thioesters easily obtained by direct hydrazinolysis of the respective glycosylated peptidyl resins and subsequent oxidation. The ligated glycopeptides can be smoothly deprotected by UV irradiation. We apply this approach to the preparation of variants of the epithelial tumor marker MUC1 carrying one or more Tn, T, or sialyl-T antigens.

A PEGylated photocleavable auxiliary mediates the sequential enzymatic glycosylation and native chemical ligation of peptides / Bello, Claudia; Wang, Shuo; Meng, Lu; Moremen, Kelley W.; Becker, Christian F. W.. - In: ANGEWANDTE CHEMIE. INTERNATIONAL EDITION. - ISSN 1433-7851. - ELETTRONICO. - 54:(2015), pp. 7711-7715. [10.1002/anie.201501517]

A PEGylated photocleavable auxiliary mediates the sequential enzymatic glycosylation and native chemical ligation of peptides

BELLO, CLAUDIA;
2015

Abstract

Research aimed at understanding the specific role of glycosylation patterns in protein function would greatly benefit from additional approaches allowing direct access to homogeneous glycoproteins. Herein the development and application of an efficient approach for the synthesis of complex homogenously glycosylated peptides based on a multifunctional photocleavable auxiliary is described. The presence of a PEG polymer within the auxiliary enables sequential enzymatic glycosylation and straightforward isolation in excellent yields. The auxiliary-modified peptides can be directly used in native chemical ligations with peptide thioesters easily obtained by direct hydrazinolysis of the respective glycosylated peptidyl resins and subsequent oxidation. The ligated glycopeptides can be smoothly deprotected by UV irradiation. We apply this approach to the preparation of variants of the epithelial tumor marker MUC1 carrying one or more Tn, T, or sialyl-T antigens.
2015
54
7711
7715
Bello, Claudia; Wang, Shuo; Meng, Lu; Moremen, Kelley W.; Becker, Christian F. W.
File in questo prodotto:
File Dimensione Formato  
anie201501517.pdf

Accesso chiuso

Descrizione: Articolo principale
Tipologia: Pdf editoriale (Version of record)
Licenza: Tutti i diritti riservati
Dimensione 2.14 MB
Formato Adobe PDF
2.14 MB Adobe PDF   Richiedi una copia
2158_1093181.pdf

accesso aperto

Tipologia: Altro
Licenza: Tutti i diritti riservati
Dimensione 819.6 kB
Formato Adobe PDF
819.6 kB Adobe PDF

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1093181
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 50
  • ???jsp.display-item.citation.isi??? 49
social impact