title: High-resolution peptide mapping of cerebrospinal fluid: a novel concept for diagnosis and research in central nervous system diseases.
abstract: Peptides, such as many hormones, cytokines and growth factors play a central role in biological processes. Furthermore, as degradation products and processed forms of larger proteins they are part of the protein turnover. Thus, they can reflect disease-related changes in an organism's homeostasis in several ways. Since two-dimensional gel electrophoresis is restricted to analysis and display of proteins with relative molecular masses above 5000, we developed Differential Peptide Display (DPD), a new technology for analysis and visualization of peptides. Here we describe its application to cerebrospinal fluid of three subjects without a disease of the central nervous system (CNS) undergoing routine myelography and of two patients suffering from a primary CNS lymphoma. Peptides with a relative molecular mass below 20000 were extracted and analysed by a combination of chromatography and mass spectrometry. The peptide pattern of a sample was depicted as a multi-dimensional peptide mass fingerprint with each peptide's position being characterized by its molecular mass and chromatographic behaviour. Such a fingerprint of a CNS sample consists of more than 6000 different signals. Data analysis of peptide patterns from patients with CNS lymphoma compared to controls revealed obvious differences regarding the peptide content of the samples. By analysing peptides within a mass range of 750-20000, DPD extends 2D gel electrophoresis, thus offering the chance to investigate CNS diseases on the level of peptides. This represents a new approach for diagnosis and possible therapy.
authors.affiliation: BioVisioN AG, Feodor-Lynen-Str. 5, D-30625 Hannover, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Heine
authors.forename: Hans Dieter
authors.initials: HD
authors.lastname: Zucht
authors.forename: Martin U
authors.initials: MU
authors.lastname: Schuhmann
authors.forename: Katharina
authors.initials: K
authors.lastname: Bürger
authors.forename: Michael
authors.initials: M
authors.lastname: Jürgens
authors.forename: Matthias
authors.initials: M
authors.lastname: Zumkeller
authors.forename: Carsten G
authors.initials: CG
authors.lastname: Schneekloth
authors.forename: Harald
authors.initials: H
authors.lastname: Hampel
authors.forename: Peter
authors.initials: P
authors.lastname: Schulz-Knappe
authors.forename: Hartmut
authors.initials: H
authors.lastname: Selle
mesh_terms: D000595:Amino Acid Sequence; D016543:Central Nervous System Neoplasms / Q000175:diagnosis*; D006801:Humans; D008223:Lymphoma / Q000175:diagnosis*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010449:Peptide Mapping / Q000379:methods*; D010455:Peptides / Q000134:cerebrospinal fluid* / Q000737:chemistry
chemical_list: D010455:Peptides