Molecular Scale Optimum Hydrophobicity To Establish an Enhanced Probe–Protein Interaction: Near-Infrared Imaging of Albumin Biosynthesis Modulation

Abstract

Albumin is the most abundant serum protein and shows variation in its synthesis rate in different physiological and pathophysiological conditions. Thus, there might be an association expected between serum albumin concentration and body health. A library of NIR probes engineered with the optimum hydrophobicity has been developed and characterized using spectroscopy techniques and was employed to understand the variation of hepatic albumin synthesis rates on physiological and pathophysiological states. Given the importance of hydrophobicity in rendering an effective interaction of small molecules with biomolecules, strategic structure interaction relationship studies led us toward the development of a potent emissive molecular probe through chemical library development. By exploration of these newly developed molecular probes, our study elegantly showed how a pathophysiological condition like the hyperinsulinemic state significantly downregulates albumin biosynthesis in HepG2 cells using fluorescence microscopy as a tool. An excellent correlation between the albumin transcript level and fluorescence intensity inside the cells has been observed. The key role of hydrophobicity resulting in an effective interaction of the probes with albumin, thus leading to strong optical signals, has been experimentally demonstrated in this report. Also, a siRNA interference technique has been utilized to establish the excellent selectivity of the developed probes with excitation as well as emission in the NIR region. We therefore have established through our experimental findings that suitable cell permeable emissive molecular markers with a high degree of albumin specificity can be used as a good optical tool for studying the effect of hyperinsulinemia on albumin biosynthesis modulation.

LVVO-Ethyl Maltol-Based Metallodrugs (L2– = Tridentate ONO Ligands): Hydrophobicity, Hydrolytic Stability, and Cytotoxicity via ROS-Mediated Apoptosis

“…The large range of the binding constants for BSA is probably due to the interaction via secondary bonds; however, this range of binding constants (10 4 –10 6 M –1 ) is suitable for potential drug-carrier complexes . Complex 2 , with K b and K q values of 6.16 × 10 5 and 1.08 × 10 14 M –1 , respectively, was established as a better quencher than the other complexes, which may be due to the interaction of the −N­(CH 2 CH 3 ) 2 group present in the ligand backbone with the active site amino acids of BSA. , Overall, other factors such as aqueous stability and hydrophobicity may also be considered in diversified bindings (for both DNA and BSA interactions) of the complexes. , Furthermore, in the case of 1 , the coligand may be lost from the [V V OL 1 (ema)] or [V V OL 1 (OH)] species and may leave vacant sites for possible interactions with proteins or DNA. However, since the complexes in 2 – 4 are well-stable in aqueous media, the mode of binding may be different in these cases.…”

Near-infrared emissive cyanine probes for selective visualization of the physiological and pathophysiological modulation of albumin levels

“…S11, ESI †), consistent with the findings reported in our previous study. 28 As hyperinsulinemia has been associated with type2 diabetes progression, often, treatment with an anti-diabetic drug is found to be effective. 51 Based on the literature reports, biguanides (belonging to the class of popular anti-diabetic drugs) have been known to regulate glucose homeostasis and insulin sensitivity.…”

“…Although a reasonable number of such probes have been previously reported for detecting and quantifying albumin, [16][17][18][19][20][21][22][23][24][25][26][27] albumin selective probes with both excitation and emission above 700 nm are still rare. 28,29 In this context, probes emitting in the near-infrared (NIR) window 700-1700 nm have gained superiority over visible range emissive probes for biological studies owing to the lower auto-fluorescence from biomolecules and biomacromolecules, higher penetration depth, less scattering of photons and high contrast images, useful for unraveling crucial biological information. 15,30 Moreover, the probe (CyG-NHS) demonstrated the ability to bind at domain-I of albumin.…”

“…Domain-I binding albumin selective biomarkers are lesser in number, 19,20 in stark contrast to the numerous domain IIA/IIIA binding probes found in the literature. [16][17][18][21][22][23][24][25][26][27][28][29] As cyanines are long known for their emission in the near-infrared (NIR) region owing to their extended conjugation, 31,32 we have developed the probe based on the cyanine scaffold having excitation (l ex = 770 nm) and emission (l em = B815 nm) in the NIR region, which, we believe, is the longest emissive albumin selective cyanine probe reported to date.…”

Explorations into the Effect of meso‐Substituents in Tricarbocyanine Dyes: A Path to Diverse Biomolecular Probes and Materials

“…Much like aminocyanine dyes, meso-oxocyanines exhibit the expected reactivity,t hat is,t hey react as nucleophiles themselves,a nd can be reacted with acid halides [48,50,53] and sulfonyl halides. [54] Rates of photobleaching are highly dependent on the protonation state of the oxocyanines.I n the keto form, photobleaching occurs at am uch lower rate compared to the parent compound. In the enol form, photobleaching occurs at am uch higher rate.…”