Mezzina Lidia, Nicosia Angelo, Barone Laura, Vento Fabiana, Mineo Placido Giuseppe
Department of Chemical Sciences and INSTM UdR of Catania, University of Catania, V.le A. Doria 6, I-95125 Catania, Italy.
Institute for Chemical and Physical Processes, National Research Council (IPCF-CNR), Viale F. Stagno d'Alcontres 37, I-98158 Messina, Italy.
Polymers (Basel). 2024 Jan 22;16(2):301. doi: 10.3390/polym16020301.
The development of nanotools for chemical sensing and macromolecular modifications is a new challenge in the biomedical field, with emphasis on artificial peptidases designed to cleave peptide bonds at specific sites. In this landscape, metal porphyrins are attractive due to their ability to form stable complexes with amino acids and to generate reactive oxygen species when irradiated by light of appropriate wavelengths. The issues of hydrophobic behavior and aggregation in aqueous environments of porphyrins can be solved by using its PEGylated derivatives. This work proposes the design of an artificial photo-protease agent based on a PEGylated mercury porphyrin, able to form a stable complex with l-Tryptophan, an amino acid present also in the lysozyme structure (a well-known protein model). The sensing and photodegradation features of PEGylated mercury porphyrin were exploited to detect and degrade both l-Trp and lysozyme using ROS, generated under green (532 nm) and red (650 nm) light lasers. The obtained system (Star3600_Hg) and its behavior as a photo-protease agent were studied by means of several spectroscopies (UV-Vis, fluorescence and circular dichroism), and MALDI-TOF mass spectrometry, showing the cleavage of lysozyme and the appearance of several short-chain residues. The approach of this study paves the way for potential applications in theranostics and targeted bio-medical therapies.
用于化学传感和大分子修饰的纳米工具的开发是生物医学领域的一项新挑战,重点是设计用于在特定位点切割肽键的人工肽酶。在这种情况下,金属卟啉因其能够与氨基酸形成稳定络合物并在适当波长的光照射下产生活性氧而具有吸引力。卟啉在水性环境中的疏水行为和聚集问题可以通过使用其聚乙二醇化衍生物来解决。这项工作提出了一种基于聚乙二醇化汞卟啉的人工光蛋白酶试剂的设计,该试剂能够与L-色氨酸形成稳定络合物,L-色氨酸也是溶菌酶结构(一种著名的蛋白质模型)中存在的氨基酸。利用聚乙二醇化汞卟啉的传感和光降解特性,使用在绿色(532 nm)和红色(650 nm)激光下产生的活性氧来检测和降解L-色氨酸和溶菌酶。通过几种光谱学(紫外可见光谱、荧光光谱和圆二色光谱)以及基质辅助激光解吸电离飞行时间质谱对所得系统(Star3600_Hg)及其作为光蛋白酶试剂的行为进行了研究,结果表明溶菌酶发生了裂解并出现了几个短链残基。本研究方法为在治疗诊断学和靶向生物医学治疗中的潜在应用铺平了道路。