Pathak Pravin, Zarandi Mohammad Amin, Zhou Xiao, Jayawickramarajah Janarthanan
Department of Chemistry, Tulane University, New Orleans, LA, United States.
Department of Biochemistry and Molecular Biology, Tulane University, New Orleans, LA, United States.
Front Chem. 2021 Nov 8;9:764137. doi: 10.3389/fchem.2021.764137. eCollection 2021.
With potential applications in materials and especially in light-responsive biomedicine that targets cancer tissue selectively, much research has focused on developing covalent conjugation techniques to tether porphyrinoid units to various biomacromolecules. This review details the key synthetic approaches that have been employed in the recent decades to conjugate porphyrinoids with oligonucleotides and peptides/proteins. In addition, we provide succinct discussions on the subsequent applications of such hybrid systems and also give a brief overview of the rapidly progressing field of porphyrin-antibody conjugates. Since nucleic acid and peptide systems vary in structure, connectivity, functional group availability and placement, as well as stability and solubility, tailored synthetic approaches are needed for conjugating to each of these biomacromolecule types. In terms of tethering to ONs, porphyrins are typically attached by employing bioorthogonal chemistry (e.g., using phosphoramidites) that drive solid-phase ON synthesis or by conducting post-synthesis modifications and subsequent reactions (such as amide couplings, hydrazide-carbonyl reactions, and click chemistry). In contrast, peptides and proteins are typically conjugated to porphyrinoids using their native functional groups, especially the thiol and amine side chains. However, bioorthogonal reactions (e.g., Staudinger ligations, and copper or strain promoted alkyne-azide cycloadditions) that utilize introduced functional groups onto peptides/proteins have seen vigorous development, especially for site-specific peptide-porphyrin tethering. While the ON-porphyrin conjugates have largely been explored for programmed nanostructure self-assembly and artificial light-harvesting applications, there are some reports of ON-porphyrin systems targeting clinically translational applications (e.g., antimicrobial biomaterials and site-specific nucleic acid cleavage). Conjugates of porphyrins with proteinaceous moieties, on the other hand, have been predominantly used for therapeutic and diagnostic applications (especially in photodynamic therapy, photodynamic antimicrobial chemotherapy, and photothermal therapy). The advancement of the field of porphyrinoid-bioconjugation chemistry from basic academic research to more clinically targeted applications require continuous fine-tuning in terms of synthetic strategies and hence there will continue to be much exciting work on porphyrinoid-biomacromolecule conjugation.
鉴于其在材料领域，尤其是在选择性靶向癌组织的光响应生物医学方面的潜在应用，许多研究都集中在开发共价连接技术，以将卟啉类单元连接到各种生物大分子上。本综述详细介绍了近几十年来用于将卟啉类与寡核苷酸和肽/蛋白质共轭的关键合成方法。此外，我们简要讨论了此类杂化系统的后续应用，并简要概述了卟啉 - 抗体共轭物这一快速发展的领域。由于核酸和肽系统在结构、连接性、官能团可用性和位置以及稳定性和溶解性方面存在差异，因此需要针对每种生物大分子类型采用定制的合成方法进行共轭。就连接到寡核苷酸而言，卟啉通常通过采用驱动固相寡核苷酸合成的生物正交化学方法（例如使用亚磷酰胺）或通过进行合成后修饰及后续反应（如酰胺偶联、酰肼 - 羰基反应和点击化学）来连接。相比之下，肽和蛋白质通常利用其天然官能团，特别是硫醇和胺侧链与卟啉类共轭。然而，利用引入到肽/蛋白质上的官能团的生物正交反应（例如施陶丁格连接以及铜或应变促进的炔 - 叠氮环加成反应）得到了蓬勃发展，特别是用于位点特异性肽 - 卟啉连接。虽然寡核苷酸 - 卟啉共轭物在很大程度上已被用于程序化纳米结构自组装和人工光捕获应用，但也有一些关于寡核苷酸 - 卟啉系统靶向临床转化应用（例如抗菌生物材料和位点特异性核酸切割）的报道。另一方面，卟啉与蛋白质部分的共轭物主要用于治疗和诊断应用（特别是在光动力疗法、光动力抗菌化疗和光热疗法中）。从基础学术研究到更具临床针对性的应用，卟啉类生物共轭化学领域的进展需要在合成策略方面不断进行微调，因此在卟啉类 - 生物大分子共轭方面将继续有许多令人兴奋的工作。
