Analysis of the degradation mechanisms of MHC class I-presented tumor antigenic peptides by high performance liquid chromatography/electrospray ionization mass spectrometry: application to the design of peptidase-resistant analogs.
Rapid Commun Mass Spectrom
; 12(9): 557-64, 1998.
Article
en En
| MEDLINE
| ID: mdl-9588030
ABSTRACT
Peptide vaccines based on the use of MHC class I restricted epitopes are currently assayed for anti-tumor and anti-viral immunotherapy. With the aim of designing minimally modified, peptidase-resistant analogs, we developed a rational approach based on a detailed understanding of the degradation mechanism of peptides in serum. Degradation of murine tumor antigen P198 and human tumor antigen MAGE-3.A1 was followed by on line high performance liquid chromatography/electrospray ionization mass spectrometry (HPLC/ESI-MS). This method provided high precision and sensitivity for rapid and direct analysis of degradation fragments in a complex mixture and, very importantly, precise identification of transient degradation fragments present at low concentrations. The design of structurally modified analogs, and the analysis of their degradation by on-line HPLC/ESI-MS, allowed us to to demonstrate the efficiency of local modifications in the protection of a given peptide bond towards a specific peptidase activity.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Péptido Hidrolasas
/
Péptidos
/
Genes MHC Clase I
Límite:
Humans
Idioma:
En
Revista:
Rapid Commun Mass Spectrom
Año:
1998
Tipo del documento:
Article
País de afiliación:
Francia