Sensitive electrospray mass spectrometry analysis of one-bead-one-compound peptide libraries labeled by quaternary ammonium salts

Remigiusz Bąchor,Magdalena Rudowska,Alicja Kluczyk,Piotr Stefanowicz,Marzena Cydzik,Zbigniew Szewczuk

doi:10.1007/s11030-012-9377-y

Remigiusz Bąchor, Magdalena Rudowska + Show 4 more

Open Access

https://doi.org/10.1007/s11030-012-9377-y

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Journal: Molecular diversity	Publication Date: Jun 28, 2012
Citations: 33	License type: cc-by

Affiliation: University of Wrocław

Abstract

A rapid and straightforward method for high-throughput analysis of single resin beads from one-bead-one-compound combinatorial libraries with high resolution electrospray ionization tandem mass spectrometry (HR ESI-MS/MS) is presented. The application of an efficient method of peptide derivatization by quaternary ammonium salts (QAS) formation increases ionization efficiency and reduces the detection limit, allowing analysis of trace amounts of compounds by ESI-MS. Peptides, synthesized on solid support, contain a new cleavable linker composed of a Peg spacer (9-aza-3,6,12,15-tetraoxa-10-on-heptadecanoic acid), lysine with ɛ-amino group marked by the N,N,N-triethylglycine salt, and methionine, which makes possible the selective cleavage by cyanogen bromide. Even a small portion of peptides derivatized by QAS cleaved from a single resin bead is sufficient for sequencing by HR ESI-MS/MS experiments. The developed strategy was applied to a small training library of α chymotrypsin substrates. The obtained results confirm the applicability of the proposed method in combinatorial chemistry.

Highlights

Rapid and efficient methods of combinatorial peptide library synthesis allow for obtaining a wide range of compounds in short time
The modification increases ionization efficiency of peptides in electrospray mass spectrometry (ESI-MS) and lowers the detection limit, whereas a fixed charge tag in MS/MS experiment is responsible for specific fragmentation patterns, which makes it very useful in the analysis of OBOC peptide libraries
This article presents synthesis and application of a new linker containing quaternary ammonium salts (QAS) group, for OBOC peptide libraries, and HR ESI-MS/MS analysis of a trace amount of peptides obtained from a single resin bead

Summary

Introduction

Rapid and efficient methods of combinatorial peptide library synthesis allow for obtaining a wide range of compounds in short time. The fundamental problem of OBOC peptide library analysis is the small amount of compound obtained from a single resin bead and insufficient ionization efficiency of some peptides for standard ESI-MS analysis.

Results

Conclusion