Automated Mass Spectrometric Sequence Determination of Cyclic Peptide Library Members

• Published in: Journal of combinatorial chemistry Vol. 5; no. 1; pp. 33 - 40
• Main Authors: Redman, James E, Wilcoxen, Keith M, Ghadiri, M. Reza
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01-01-2003
• Subjects: Automation; Mass Spectrometry; Peptide Library; Peptides, Cyclic - analysis; Peptides, Cyclic - chemical synthesis; Peptides, Cyclic - genetics; Sequence Analysis, Protein - instrumentation; Sequence Analysis, Protein - methods; Software
• ISSN: 1520-4766; 1520-4774
• DOI: 10.1021/cc0200639

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-α-peptides.