Synthesis and structural characterization of bioactive peptide conjugates using thioether linkage approaches
Article first published online: 7 JUL 2004
Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd.
Journal of Peptide Science
Volume 10, Issue 12, pages 701–713, December 2004
How to Cite
Mezö, G., Manea, M., Jakab, A., Kapuvári, B., Bösze, S., Schlosser, G., Przybylski, M. and Hudecz, F. (2004), Synthesis and structural characterization of bioactive peptide conjugates using thioether linkage approaches. J. Peptide Sci., 10: 701–713. doi: 10.1002/psc.583
- Issue published online: 23 NOV 2004
- Article first published online: 7 JUL 2004
- Manuscript Accepted: 19 MAR 2004
- Manuscript Received: 19 FEB 2004
- Hungarian National Science Fund. Grant Numbers: OTKA T032425, T043576, T043538.
- peptide conjugates;
- tetratuftsin derivative;
- thioether bond;
- HSV epitope peptide;
- β-amyloid epitope;
Applications of cysteine-insertion and thioether linkage approaches to the preparation of a number of bioactive peptide conjugates are reported. Peptides containing epitopes from (i) herpes simplex virus type 1 glycoprotein D, (ii) a specific N-terminal β-amyloid epitope recognized by therapeutically active antibodies, and (iii) a GnRH-III peptide from sea lamprey with antitumour activity, were elongated with Cys residues and attached to a chloroacetylated tetratuftsin derivative carrier via a thioether linkage either directly, or by insertion of a spacer. The structures and molecular homogeneity of all the peptide conjugates were ascertained by HPLC, MALDI and electrospray mass spectrometry. The use of a spacer such as an oligoglycine or GFLG-tetrapeptide gave an increased yield in the conjugation reaction and enhanced reaction rates. In the formation of cysteinyl-thioether linkages, it was found that the position of flanking Cys residues markedly influenced the conjugation reaction and the formation of intermolecular epitope disulfide-dimers. C-terminal Cys residues gave thioether conjugates with significantly diminished epitope-dimerization, while Cys at the N-terminal caused rapid disulfide-dimerization, thereby preventing efficient conjugation. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd.