Mass spectrometric sequencing of individual peptides from combinatorial libraries via specific generation of chain-terminated sequences |
| |
Authors: | Hoffmann Christian Blechschmidt Dierk Krüger Ralf Karas Michael Griesinger Christian |
| |
Affiliation: | Institute of Organic Chemistry, University of Frankfurt, Marie-Curie-Strasse 11, D-60439 Frankfurt am Main, Germany. . |
| |
Abstract: | Combinatorial peptide libraries are a versatile tool for drug discovery. On-bead assays identify reactive peptides by enzyme-catalyzed staining and, usually, sequencing by Edman degradation. Unfortunately, the latter method is expensive and time-consuming and requires free N termini of the peptides. A method of rapid and unambiguous peptide sequencing by utilizing synthesis-implemented generation of termination sequences with subsequent matrix-assisted laser desorption ionization time of flight (MALDI-TOF) mass spectrometric analysis is introduced here. The required capped sequences are determined and optimized for a specific peptide library by a computer algorithm implemented in the program Biblio. A total of 99.7% of the sequences of a heptapeptide library sample could be decoded utilizing a single bead for each spectrum. To synthesize these libraries, an optimized capping approach has been introduced. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|