Abstract
Site-specific conjugation of proteins is currently required to produce homogenous derivatives for medicine applications. Proteins derivatized at specific positions of the polypeptide chain can actually show higher stability, superior pharmacokinetics, and activity in vivo, as compared with conjugates modified at heterogeneous sites. Moreover, they can be better characterized regarding the composition of the derivatization sites as well as the conformational and activity properties. To this aim, several site-specific derivatization approaches have been developed. Among these, enzymes are powerful tools that efficiently allow the generation of homogenous protein–drug conjugates under physiological conditions, thus preserving their native structure and activity. This review will summarize the progress made over the last decade on the use of enzymatic-based methodologies for the production of site-specific labeled immunoconjugates of interest for nuclear medicine. Enzymes used in this field, including microbial transglutaminase, sortase, galactosyltransferase, and lipoic acid ligase, will be overviewed and their recent applications in the radiopharmaceutical field will be described. Since nuclear medicine can benefit greatly from the production of homogenous derivatives, we hope that this review will aid the use of enzymes for the development of better radio-conjugates for diagnostic and therapeutic purposes.
Highlights
Bioconjugation techniques that exploit enzymes are a growing field of protein chemistry due to the interest to produce conjugates of proteins with small molecules or macromolecules for applications in research as well as in the biotechnological and pharmaceutical industries [1]
Traditional protein conjugation techniques rely mainly on the chemical derivatization of Lys residues with the drawback that since several Lys are present in a single protein, the reaction product is heterogeneous in respect to the site of conjugation
Nuclear molecular imaging (MI) with radiolabeled proteins based on therapeutic monoclonal antibodies (mAb) or on different formats derived from immunoglobulin G (IgG) and from alternative scaffolds is utilized as a scouting procedure before radiotherapy
Summary
Bioconjugation techniques that exploit enzymes are a growing field of protein chemistry due to the interest to produce conjugates of proteins with small molecules or macromolecules for applications in research as well as in the biotechnological and pharmaceutical industries [1]. Nuclear molecular imaging (MI) with radiolabeled proteins based on therapeutic mAb or on different formats derived from immunoglobulin G (IgG) and from alternative scaffolds is utilized as a scouting procedure before radiotherapy It allows for confirming the tumor targeting and accurately estimating the radiation dose delivered to both tumor and healthy tissues, giving an important help for the selection of the candidates for radioimmunotheraphy (RIT). In this connection, while the development of new specific mAb and related is fundamental to target different tumors and more histotypes for the same tumor, the development of methods that allow for an efficient and site-specific derivatization of proteins in physiological conditions (
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