title: Composition of the peptide fraction in human blood plasma: database of circulating human peptides.
abstract: A database was established from human hemofiltrate (HF) that consisted of a mass database and a sequence database, with the aim of analyzing the composition of the peptide fraction in human blood. To establish a mass database, all 480 fractions of a peptide bank generated from HF were analyzed by MALDI-TOF mass spectrometry. Using this method, over 20000 molecular masses representing native, circulating peptides were detected. Estimation of repeatedly detected masses suggests that approximately 5000 different peptides were recorded. More than 95% of the detected masses are smaller than 15000, indicating that HF predominantly contains peptides. The sequence database contains over 340 entries from 75 different protein and peptide precursors. 55% of the entries are fragments from plasma proteins (fibrinogen A 13%, albumin 10%, beta2-microglobulin 8.5%, cystatin C 7%, and fibrinogen B 6%). Seven percent of the entries represent peptide hormones, growth factors and cytokines. Thirty-three percent belong to protein families such as complement factors, enzymes, enzyme inhibitors and transport proteins. Five percent represent novel peptides of which some show homology to known peptide and protein families. The coexistence of processed peptide fragments, biologically active peptides and peptide precursors suggests that HF reflects the peptide composition of plasma. Interestingly, protein modules such as EGF domains (meprin Aalpha-fragments), somatomedin-B domains (vitronectin fragments), thyroglobulin domains (insulin like growth factor-binding proteins), and Kazal-type inhibitor domains were identified. Alignment of sequenced fragments to their precursor proteins and the analysis of their cleavage sites revealed that there are different processing pathways of plasma proteins in vivo.
authors.affiliation: Lower Saxony Institute for Peptide Research, Hannover, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Richter
authors.forename: P
authors.initials: P
authors.lastname: Schulz-Knappe
authors.forename: M
authors.initials: M
authors.lastname: Schrader
authors.forename: L
authors.initials: L
authors.lastname: Ständker
authors.forename: M
authors.initials: M
authors.lastname: Jürgens
authors.forename: H
authors.initials: H
authors.lastname: Tammen
authors.forename: W G
authors.initials: WG
authors.lastname: Forssmann
mesh_terms: D000595:Amino Acid Sequence; D002853:Chromatography, Liquid / Q000379:methods; D016208:Databases, Factual; D005340:Fibrinogen / Q000737:chemistry / Q000302:isolation & purification; D006440:Hemofiltration; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000097:blood* / Q000737:chemistry / Q000302:isolation & purification; D017386:Sequence Homology, Amino Acid; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D010455:Peptides; D005340:Fibrinogen