Top-down peptidomics of bodily fluids

Blood is a complex liquid tissue including a corpuscular and a non-corpuscular fractions and represent the major connection between cells and tissues of an organism, allowing transport of oxygen and many molecules (i. e. hormones, amino acids, carbohydrates, lipids, vitamins, mineral salts and water), and the reject of waste substances.

The proteome/peptidome of a blood sample is directly linked to the metabolic state and utilizable to provide information on the physiological and/or pathological processes occurring in the body. The proteins and peptides present in serum and plasma, the non-corpuscular blood fractions, are a combination of those playing circulatory functions and those secreted or released into the circulation from cells both during normal biological events and in diseases [6].

Because serum and plasma are the most available clinical samples, they represent one of the most convenient choices for minimal-invasive detection of peptides potentially relevant as specific disease-biomarkers. Naturally occurring peptides typically derive from cleavages of the most abundant full-length proteins as a result of numerous proteases activity contained in these fluids or produced by cells [7].

As reported, a high number of peptides are only present in serum and not detectable in plasma. In fact, more than 40% of the peptides detected in serum are generated by ex vivo processes during specimen collection and preparation, introducing peptide signals which have to be interpreted with prudence [8]. Serum generation is associated with the coagulation cascade and the activation of complement system, processes leading cell lysis and multiproteinase activation, which cleave various proteins producing a lot of peptides. Moreover, peptid...

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...eptidome profile 12 peptide candidates have been suggested as cancer biomarkers [35]. Among them, eight are reported as fibrinopeptide A (FPA) and FPA derived peptides (fragments 2-16, 3-15, 3-16, 4-16, 5-16, 6-15, 6-16, 1-16), two belonging to apolipoprotein A-IV (fragments 273-283 and 271-283), one to limbin (fragment 306-313) and one to amiloride-sensitive cation channel 4 (fragment 613-624).

In summary, plasma and serum top-down peptidomic analysis could represent a powerful strategy for the comprehension of biological processes, such as signal transmission between cells, circulation and transport of several molecules and the development of diseases. The identification of serum/plasma biomarkers diseases, especially cancer disease, is the first goal of all the research laboratories involved in the Plasma Proteome Project of the Human Proteome Organization [11].