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Quantification of bioactive peptides by mass spectrometry - Applicability in drug discovery

Objective

The study of pharmacologically active peptides is central to the understanding of disease and to the development of novel therapies. It would be advantageous to monitor the fate of bioactive peptides following their administration or the modulation of endogenous factors (e.g. peptide hormones) affected by the administration of pharmacological agent. Measurement of administered compounds in plasma is a mature field. However, measurement of pharmacologically active peptides, such as Glucose-dependent insulinotropic peptide (GIP) and the melanocortin analogue Melanotan-II (MT-II) presents particular problems for quantitative mass spectrometry, including challenges from selectivity and sensitivity perspectives. Current approaches towards peptide quantification in biological fluids include immunoassays or uses of mass spectrometric techniques. Immunoassays, although sensitive, lack the necessary selectivity for distinction between peptide and metabolites. Modified molecules induced by metabolic transformations (e.g. N- or C-terminal truncation of the peptide) might not be differentiated by the antibody used in the assay, leading to cross-reactivity.

However, although it is generally accepted that mass spectrometry is an ideal technique for the quantification of trace levels of analytes in biological fluids, immunological techniques are still characterized by better limits of detection. In this application we propose to contribute to the field of quantification of peptides by mass spectrometry by pursuing novel approaches on selective peptides for which limits of quantification have been previously established. If we succeed we will demonstrate the applicability of the approaches in vivo models.

In the future our knowledge (improved mass spectrometric approaches) can be extended to other bioactive peptides in studies that address drug target validation, the development of new therapies and the discovery and validation of biomarkers.

Call for proposal

FP6-2004-MOBILITY-12
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Coordinator

FOUNDATION FOR BIOMEDICAL RESEARCH OF THE ACADEMY OF ATHENS
Address
Soranou Efesiou 4
Athens
Greece