title: Chemical linkage to injected tissues is a distinctive property of oxidized avidin.
abstract: We recently reported that the oxidized avidin, named AvidinOX®, resides for weeks within injected tissues as a consequence of the formation of Schiff's bases between its aldehyde groups and tissue protein amino groups. We also showed, in a mouse pre-clinical model, the usefulness of AvidinOX for the delivery of radiolabeled biotin to inoperable tumors. Taking into account that AvidinOX is the first oxidized glycoprotein known to chemically link to injected tissues, we tested in the mouse a panel of additional oxidized glycoproteins, with the aim of investigating the phenomenon. We produced oxidized ovalbumin and mannosylated streptavidin which share with avidin glycosylation pattern and tetrameric structure, respectively and found that neither of them linked significantly to cells in vitro nor to injected tissues in vivo, despite the presence of functional aldehyde groups. The study, extended to additional oxidized glycoproteins, showed that the in vivo chemical conjugation is a distinctive property of the oxidized avidin. Relevance of the high cationic charge of avidin into the stable linkage of AvidinOX to tissues is demonstrated as the oxidized acetylated avidin lost the property. Plasmon resonance on matrix proteins and cellular impedance analyses showed in vitro that avidin exhibits a peculiar interaction with proteins and cells that allows the formation of highly stable Schiff's bases, after oxidation.
authors.affiliation: Department of Immunology, Sigma-Tau SpA, Pomezia, Rome, Italy. rita.desantis@sigma-tau.it
authors.forename: Rita
authors.initials: R
authors.lastname: De Santis
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Anastasi
authors.forename: Angela
authors.initials: A
authors.lastname: Pelliccia
authors.forename: Antonio
authors.initials: A
authors.lastname: Rosi
authors.forename: Claudio
authors.initials: C
authors.lastname: Albertoni
authors.forename: Antonio
authors.initials: A
authors.lastname: Verdoliva
authors.forename: Fiorella
authors.initials: F
authors.lastname: Petronzelli
authors.forename: Valeria
authors.initials: V
authors.lastname: D'Alessio
authors.forename: Serenella
authors.initials: S
authors.lastname: Serani
authors.forename: Carlo Antonio
authors.initials: CA
authors.lastname: Nuzzolo
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001360:Avidin / Q000378:metabolism*; D045744:Cell Line, Tumor; D002645:Chickens; D006023:Glycoproteins / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D010047:Ovalbumin / Q000378:metabolism; D011485:Protein Binding; D019809:Streptavidin / Q000378:metabolism; D020349:Surface Plasmon Resonance
chemical_list: D006023:Glycoproteins; D001360:Avidin; D010047:Ovalbumin; D019809:Streptavidin