CHEMICAL PROTEOMICS FOR TARGET DISCOVERY

CHEMICAL PROTEOMICS FOR TARGET DISCOVERY

The development of antibody-based therapeutics crucially relies on the identification of target antigens, which are specifically expressed at the site of disease and which are readily accessible for agents coming from the bloodstream.
In collaboration with ETH Zürich, Philochem has pioneered chemical proteomics methods for the characterization of accessible markers of pathology, which can be drugged by antibodies. In a simple set-up, cell lines can be submitted to surface biotinylation, followed by capture on streptavidin resin and mass spectrometric analysis of tryptic peptides [8, 12]. In a more complex set up, in vivo biotinylation procedures of rodent models of pathology enable the chemical proteomic characterization of vascular proteins, in health an in disease [3, 4, 5, 6, 13]. The technology has been extended to the ex vivo perfusion of surgically-resected human organs with cancer [7, 9, 10].

SELECTED REFERENCES

Elia et al. (2014) J Proteomics. 107:50-5, review;
Neri and Supuran (2011) Nat. Rev. Drug Discov. 10:767-77, review;
Fugmann et al., (2011) Kidney Int. 80:272-81;
Roesli et al., (2011) J. Proteomics 74:539-46;
Schliemann et al., (2010) Blood 115:736-44;
Borgia et al., (2010) Cancer Res. 70:309-18;
Fugmann et al., (2010) Proteomics 10:2631-43;
Rösli et al. (2008) Methods Mol Biol. 418:89-100;
Conrotto et al. (2008) Int J Cancer. 123:2856-64;
Castronovo et al. (2006) Mol. Cell. Proteomics 5:2083-2091;
Brack et al. (2006) Clin. Cancer Res. 12:3200-8;
 Scheurer et al. (2005) Proteomics 5:2718-2728;
Rybak et al. (2005) Nat. Methods 2:291-298;
Neri and Bicknell (2005) Nat. Rev. Cancer 5:436-46, review.

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