School of Chemical Sciences, Indian Institute of Technology Mandi, Kamand-175005, Himachal Pradesh, India.
School of Bioscience and Bioengineering, Indian Institute of Technology Mandi, Kamand-175005, Himachal Pradesh, India.
J Mater Chem B. 2024 May 8;12(18):4441-4450. doi: 10.1039/d3tb01938a.
In this study, we report a small molecule optical marker BI-CyG derived from the structural engineering of a cyanine scaffold. The developed probe offers suitable advantages over existing cyanine-based albumin specific probes in terms of its excitation and emission wavelengths, which are 760 and 830-832 nm, respectively. Structural tuning of the cyanine architecture leading to extended π-conjugation and resulting in a suitable bathochromic shift in the emission wavelength of the probe is represented in this study. The probe besides emitting in the NIR region, also possesses the desirable characteristics of being a potential target selective optical marker, as established from various biophysical studies. Molecular modelling and simulation studies provided critical insights into the binding of the probe in the protein microenvironment, which was further supported by experimental studies. The probe displayed intracellular albumin selectivity and was utilized for demonstrating alteration in albumin levels in pathological states such as hyperglycemia in hepatic cells. The present study also sheds some light on using BI-CyG as an imaging probe and on the role of metformin as a suitable drug for balancing hyperglycemia-induced reduced intra-hepatic albumin levels. The study, thus, attempts to highlight the structural derivatization of cyanine to afford a potential probe for serum albumin and its deployment to image altering albumin levels in an induced pathological condition, hyperglycemia.
在这项研究中,我们报告了一种小分子光学标记物 BI-CyG,它源自对菁染料支架的结构工程改造。与现有的基于菁染料的白蛋白特异性探针相比,该开发的探针在激发和发射波长方面具有合适的优势,分别为 760nm 和 830-832nm。本研究代表了对菁染料结构的结构调整,导致扩展的π共轭,并导致探针发射波长的合适红移。该探针除了在近红外区域发射外,还具有作为潜在靶标选择性光学标记物的理想特性,这是从各种生物物理研究中确定的。分子建模和模拟研究提供了对探针在蛋白质微环境中结合的关键见解,这得到了实验研究的进一步支持。该探针在细胞内显示出白蛋白选择性,并用于证明病理状态下白蛋白水平的变化,如肝细胞中的高血糖。本研究还揭示了使用 BI-CyG 作为成像探针以及二甲双胍作为平衡高血糖诱导的肝内白蛋白水平降低的合适药物的作用。因此,该研究试图强调菁染料的结构衍生化以提供潜在的血清白蛋白探针,并将其用于在诱导的病理条件下成像改变的白蛋白水平,如高血糖。