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      OXavidin for Tissue Targeting Biotinylated Therapeutics

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          Abstract

          Avidin is a glycoprotein from hen egg white that binds biotin with very high affinity. Here we describe OXavidin, a product containing aldehyde groups, obtained by ligand-assisted sugar oxidation of avidin by sodium periodate. OXavidin chemically reacts with cellular and tissue proteins through Schiff's base formation thus residing in tissues for weeks while preserving the biotin binding capacity. The long tissue residence of OXavidin as well as that of OXavidin/biotinylated agent complex occurs in normal and neoplastic tissues and immunohistochemistry shows a strong and homogenous stromal localization. Once localized in tissue/tumor, OXavidin becomes an “artificial receptor” for intravenous injected biotin allowing tumor targeting with biotinylated therapeutics like radioisotopes or toxins. Moreover, present data also suggest that OXavidin might be useful for the homing of biotinylated cells. Overall, OXavidin exhibits a remarkable potential for many different therapeutic applications.

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          Most cited references25

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          Protein and nucleotide damage by glyoxal and methylglyoxal in physiological systems--role in ageing and disease.

          Glycation of proteins, nucleotides and basic phospholipids by glyoxal and methylglyoxal--physiological substrates of glyoxalase 1--is potentially damaging to the proteome, genome and lipidome. Glyoxalase 1 suppresses glycation by these alpha-oxoaldehyde metabolites and thereby represents part of the enzymatic defence against glycation. Albert Szent-Györgyi pioneered and struggled to understand the physiological function of methylglyoxal and the glyoxalase system. We now appreciate that glyoxalase 1 protects against dicarbonyl modifications of the proteome, genome and lipome. Latest research suggests there are functional modifications of this process--implying a role in cell signalling, ageing and disease.
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            Therapeutic antibody fragments with prolonged in vivo half-lives.

            Antibody fragments can be isolated rapidly using techniques such as phage display and can be expressed to high levels in microbial systems. However, to date such antibody fragments have been of limited use for many therapeutic applications because they are rapidly cleared from the body. We present a strategy for the site-specific chemical modification of antibody fragments with polyethylene glycol, which results in the production of antibody fragments with long in vivo half-lives and full retention of antigen-binding properties. This technology should allow more rapid and economical production of therapeutic antibodies for chronic disease therapy.
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              THE PROPERTIES OF STREPTAVIDIN, A BIOTIN-BINDING PROTEIN PRODUCED BY STREPTOMYCETES.

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                Author and article information

                Journal
                J Biomed Biotechnol
                JBB
                Journal of Biomedicine and Biotechnology
                Hindawi Publishing Corporation
                1110-7243
                1110-7251
                2009
                10 January 2010
                : 2009
                : 921434
                Affiliations
                1Immunology Department, Sigma-Tau SpA R&D, Pomezia, 00040 Rome, Italy
                2European Institute of Oncology, 20141 Milan, Italy
                3Tecnogen SpA, 81013 Caserta, Italy
                4Sigma-Tau SpA R&D, Pomezia, 00040 Rome, Italy
                Author notes

                Recommended by Eric W. Lam

                Article
                10.1155/2009/921434
                2814378
                20130784
                45632c66-a3d6-46aa-82a7-ed23ea583e69
                Copyright © 2009 Rita De Santis et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 21 July 2009
                : 16 October 2009
                Categories
                Research Article

                Molecular medicine
                Molecular medicine

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