Encapsulation of catalytic functionalities into apoferritin for prodrug delivery.

项目概述：该项目致力于设计一种能够通过水解来裂解酯、氨基甲酸酯和酰胺键的人造酶。这些实体将用于将前体药物转化为具有药理活性的衍生物。酶解在前体药物活化中起着重要的作用。这种方法的创新之处在于利用人工酶在药物治疗中实现高度特异性的靶向，以改善医疗治疗的疗效和毒理学特征。目的是利用蛋白质载铁蛋白作为生物相容的支架来结合化学催化剂。铁蛋白是一种铁存储纳米粒子，已被广泛研究用于癌症治疗和诊断。铁的去除将铁蛋白转化为载脂蛋白笼子。最终，该项目将提供一种经过改造的载铁蛋白，具有前药物激活所需的催化活性。目的：设计一种能够催化含酯、氨基甲酸酯和酰胺基团的化合物的人工酶。方法：蛋白质工程和化学合成。新奇：使用人工酶作为治疗工具。

Project summary: This project is focused on the design of an artificial enzyme able to cleave ester, carbamate and amide bonds by hydrolysis. These entities will be used to convert prodrug precursors into their pharmacologically active derivatives. Enzymatic hydrolysis plays an important role in prodrug activation. The novelty of this approach is the exploitation of artificial enzymes for the achievement of highly specific targeting in pharmacological therapies in order to improve the efficacy and the toxicological profile of medical treatments. The aim is to use the protein apoferritin, as a biocompatible scaffold for the incorporation of chemical catalysts. Ferritin is an iron storage nanoparticle which has been widely studied for cancer therapeutics and diagnostics. Removal of iron turns ferritin into the apoferritin cage. Ultimately, this project will deliver an engineered apoferritin with the catalytic activity required for prodrugs activation. Objective: design of an artificial enzyme able to catalyse the hydrolysis of compounds containing ester, carbamate and amide groups.Approach: protein engineering and chemical synthesis.Novelty: Use of artificial enzyme as therapeutic tool.