title: Automated mass spectrometric sequence determination of cyclic peptide library members.
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.
authors.affiliation: Department of Chemistry, and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Redman
authors.forename: Keith M
authors.initials: KM
authors.lastname: Wilcoxen
authors.forename: M Reza
authors.initials: MR
authors.lastname: Ghadiri
mesh_terms: D001331:Automation; D013058:Mass Spectrometry; D019151:Peptide Library; D010456:Peptides, Cyclic / Q000032:analysis* / Q000138:chemical synthesis / Q000235:genetics; D020539:Sequence Analysis, Protein / Q000295:instrumentation* / Q000379:methods; D012984:Software
chemical_list: D019151:Peptide Library; D010456:Peptides, Cyclic