Institute of Condensed Matter Chemistry and Technologies for Energy ICMATE-CNR, Corso Stati Uniti, 4, I-35127 Padova, Italy.
Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Via Marzolo, 5, I-35131 Padova, Italy.
Molecules. 2021 Jun 8;26(12):3492. doi: 10.3390/molecules26123492.
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.
目前，为了生产用于医学应用的均质衍生物，需要对蛋白质进行位点特异性缀合。与在异质位点修饰的缀合物相比，在多肽链的特定位置衍生的蛋白质实际上可以显示更高的稳定性、更优的药代动力学和体内活性。此外，它们可以更好地描述衍生化位点的组成以及构象和活性特性。为此，已经开发了几种位点特异性衍生化方法。其中，酶是有效的工具，可以在生理条件下高效地生成均质的蛋白质-药物缀合物，从而保持其天然结构和活性。本文综述了过去十年中利用基于酶的方法生产用于核医学的感兴趣的位点特异性标记免疫缀合物方面的进展。本文将综述该领域使用的酶，包括微生物转谷氨酰胺酶、连接酶、半乳糖基转移酶和硫辛酸连接酶，并描述它们在放射性药物领域的最新应用。由于核医学可以从同质衍生物的生产中大大受益，我们希望本文的综述将有助于酶的使用，以开发用于诊断和治疗目的的更好的放射性缀合物。
