Automated mass spectrometric sequence determination of cyclic peptide library members

J Comb Chem. 2003 Jan-Feb;5(1):33-40. doi: 10.1021/cc0200639.

Abstract

Cyclic peptides have come under scrutiny as potential antimicrobial therapeutic agents. Combinatorial split-and-pool synthesis of cyclic peptides can afford single compound per well libraries for antimicrobial screening, new lead identification, and construction of quantitative structure-activity relationships (QSAR). Here, we report a new sequencing protocol for rapid identification of the members of a cyclic peptide library based on automated computer analysis of mass spectra, obviating the need for library encoding/decoding strategies. Furthermore, the software readily integrates with common spreadsheet and database packages to facilitate data visualization and archiving. The utility of the new MS-sequencing approach is demonstrated using sonic spray ionization ion trap MS and MS/MS spectrometry on a single compound per bead cyclic peptide library and validated with individually synthesized pure cyclic D,L-alpha-peptides.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Automation
  • Mass Spectrometry
  • Peptide Library*
  • Peptides, Cyclic / analysis*
  • Peptides, Cyclic / chemical synthesis
  • Peptides, Cyclic / genetics
  • Sequence Analysis, Protein / instrumentation*
  • Sequence Analysis, Protein / methods
  • Software

Substances

  • Peptide Library
  • Peptides, Cyclic