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Mol Pharm. 2013 May 6;10(5):1998-2007. doi: 10.1021/mp400026y. Epub 2013 Apr 10.

Mass spectrometry-guided optimization and characterization of a biologically active transferrin-lysozyme model drug conjugate.

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  • 1Department of Chemistry, University of Massachusetts Amherst, Amherst, Massachusetts 01003, United States.

Abstract

Transferrin is a promising drug carrier that has the potential to deliver metals, small organic molecules and therapeutic proteins to cancer cells and/or across physiological barriers (such as the blood-brain barrier). Despite this promise, very few transferrin-based therapeutics have been developed and reached clinical trials. This modest success record can be explained by the complexity and heterogeneity of protein conjugation products, which also pose great challenges to their analytical characterization. In this work, we use lysozyme conjugated to transferrin as a model therapeutic that targets the central nervous system (where its bacteriostatic properties may be exploited to control infection) and develop analytical protocols based on electrospray ionization mass spectrometry to characterize its structure and interactions with therapeutic targets and physiological partners critical for its successful delivery. Mass spectrometry has already become an indispensable tool facilitating all stages of the protein drug development process, and this work demonstrates the enormous potential of this technique in facilitating the development of a range of therapeutically effective protein-drug conjugates.

PMID:
23534953
[PubMed - indexed for MEDLINE]
PMCID:
PMC3647025
Free PMC Article
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