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用于组织靶向生物素化治疗药物的氧抗生物素蛋白

OXavidin for tissue targeting biotinylated therapeutics.

作者信息

De Santis Rita, Albertoni Claudio, Rosi Antonio, Leoni Barbara, Petronzelli Fiorella, D'Alessio Valeria, Nucera Eleonora, Salvatori Giovanni, Paganelli Giovanni, Verdoliva Antonio, Carminati Paolo, Nuzzolo Carlo Antonio

机构信息

Immunology Department, Sigma-Tau SpA R&D, Pomezia, 00040 Rome, Italy.

出版信息

J Biomed Biotechnol. 2009;2009:921434. doi: 10.1155/2009/921434. Epub 2010 Jan 10.

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.

摘要

抗生物素蛋白是一种来自鸡蛋白的糖蛋白,它能以非常高的亲和力结合生物素。在此,我们描述了氧化抗生物素蛋白(OXavidin),一种含有醛基的产物,它是通过高碘酸钠对抗生物素蛋白进行配体辅助糖氧化反应而获得的。氧化抗生物素蛋白通过席夫碱的形成与细胞和组织蛋白发生化学反应,从而在组织中留存数周,同时保持生物素结合能力。氧化抗生物素蛋白以及氧化抗生物素蛋白/生物素化试剂复合物在正常组织和肿瘤组织中都有较长的组织留存时间,免疫组织化学显示其在基质中呈强而均匀的定位。一旦定位在组织/肿瘤中,氧化抗生物素蛋白就成为静脉注射生物素的“人工受体”,从而能够利用放射性同位素或毒素等生物素化治疗药物实现肿瘤靶向。此外,目前的数据还表明氧化抗生物素蛋白可能有助于生物素化细胞的归巢。总体而言,氧化抗生物素蛋白在许多不同的治疗应用中显示出显著的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5af0/2814378/f4adbcf3a409/JBB2009-921434.001.jpg

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