“OMICS” | Combinatorial Libraries for Capturing the “Hidden” Proteome

Abstract

One rational and easy way for detecting low-abundance species in proteomes is to reduce the large concentration difference between proteins; this is now accomplished by using solid-phase libraries of combinatorial ligands. One of them is known under the name of ‘Protein Equalizer™ technology’ (Ciphergen Biosystems, Inc., Fremont, CA, USA). This comprises a very large collection of combinatorial peptides coupled to porous beads, each of them acting as very small affinity columns. When these beads are contacted with complex proteomes (e.g., human urines and sera, egg white, and any cell lysate) of widely differing protein composition and relative abundances, they are able to ‘equalize’ the protein population by sharply reducing the concentration of the most abundant components while simultaneously enhancing the concentration of the most dilute components. It is felt that this novel method could offer a strong step forward in bringing the ‘unseen proteome’ (due to either low abundance and/or presence of interferences) within the detection capabilities of current proteomics detection methods. Examples are given of equalization of human urine and sera samples, resulting in the discovery of a host of proteins never reported before. Additionally, these beads can be used for removing host cell proteins from purified recombinant proteins or protein purified from natural sources that are intended for human consumption. It represents also an extremely attractive way for discovering protein biomarker of diagnostic and therapeutic interest that are very dilute and below the detection limit of current methods.