Combinatorial peptide library electrospray mass spectrometry

BE Winger, JE Campana. Characterization of combinatorial peptide libraries by electrospray ionization Fourier transform mass spectrometry. Rapid Commun Mass Spectrom 10 1811-1813, 1996. 

To synthesize highly diverse libraries, carrying more than six degenerated sequence positions (X), several methods using premixed mixtures of amino acids for the introduction of X positions in the sequence have been described [12]. Obviously, the frequency of each amino acid in a X position is influenced by the composition of the premixed amino acid mixture, the chemistry applied for coupling as well as by the nature of the solid support. The synthetic peptide libraries have been analyzed by electrospray mass spectrometry and pool sequencing [13,14]. Due to their stoichiometry, peptides from extremely diverse combinatorial collections are only partially accessible for biological assays [12]. 

The past years have seen the development of two important ionization techniques electrospray ionization (ESI) and matrix-assisted laser desorption (MALDI), which have been used especially in conjunction with quadrupole, time of flight (TOF) and ion cyclotron (IC) analyzers. Both ionization techniques have revolutionized the essence of mass spectrometry itself, radically increasing the upper mass limit and thus the applicability of the mass spectrometric technique and indirectly affecting the endeavors for improved resolution and sensitivity. With these techniques, the analysis of peptides, proteins and oligonucleotides has become possible. The aim of this chapter is to demonstrate the capabilities of these techniques, especially electrospray mass spectrometry in conjunction with HPLC techniques, for the analysis of combinatorially generated compounds and libraries, and to exemplify and discuss both the potentials and limits of these analytical techniques. 

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