Human serum albumin is perceived to be the most abundant protein in human blood plasma and functions as a major carrier of different enzymes and drugs inside human body. The present article puts in an effort to demonstrate the attitude adopted by human serum albumin towards a potential therapeutic luminophore 4-(2-Hydroxyethyl)-10-phenyl-3,4,6,7,8,10-hexahydro-1H-cyclopenta[g]furo[3,4-b]quinoline-1-one (HPFQ). HPFQ is a prodigy from azapodophyllotoxin class of compounds, which have been synthesized from the perspective of improved bioactivity than its prologue podophyllotoxins. While, HPFQ has proved to be highly bioactive against most cancer cell lines with best GI50 values of <0.1 µM for a major number of cell lines; it also showed terrific fluorescent properties throughout the polarity scale, worthy of a promising imaging agent. The binding mechanism of HPFQ with HSA has been established by combining in vitro spectroscopic techniques, in silico molecular docking and induced fit docking (IFD). The competitive site-binding studies demonstrated that the otherwise anion-receptor sudlow site I of HSA nurtures neutral HPFQ with prudent affinity (Binding constant, Kb = 0.74 × 105 M-1). The time-resolve fluorescence studies reveal an appreciable reduction in HSA average radiative lifetime against an increase in HPFQ concentration and provided evidence for Forster's resonance energy transfer (FRET) being responsible for the dominant quenching mechanism, escorted by minor structural deformations in the backbone of protein structure. HPFQ institutes itself near Trp-214 within protein matrix, and subsequently the "hydrophobic amino acids" dominated cybotactic environment of Trp-214 experiences a reduction in the micropolarity. The allosteric modulation triggered by the stronger association of HPFQ with HSA leads towards minor deformation in secondary structure of protein. Sudlow site I of HSA proficiently embraces a favourable conformation like malleable dough to furnish space for arriving bioactive HPFQ molecule. HPFQ is also believed to administer the conformational regulation in HSA domain by affecting inter-conversion of HSA rotamers, which may prove to be an enlightening area to decode the preferable interaction between them. The juxtaposed spectroscopic research described herein is expected to embolden design of azapodophyllotoxin based anti-proliferative clinical agents for efficient in vivo bio-distribution employing HSA-centred drug delivery and administration systems.

中文翻译：

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人类血清白蛋白中Trp-214内在旋转异构体群体的转换：对将治疗性生物有机发光体氮杂鬼臼毒素引入低位I的后果的见解。

人血清白蛋白被认为是人血浆中最丰富的蛋白质，并作为人体内各种酶和药物的主要载体。本文致力于证明人血清白蛋白对潜在的治疗性发光体4-（2-羟乙基）-10-苯基-3,4,6,7,8,10-六氢-1H-环戊烯所采取的态度[g]呋喃[3,4-b]喹啉-1-酮（HPFQ）。HPFQ是来自apopodophyllotoxin类化合物的奇迹，从其生物活性比其序言鬼臼毒素更好的角度出发，已经合成了HPFQ。同时，HPFQ已被证明对大多数癌细胞具有高生物活性，大多数细胞系的最佳GI50值<0.1 µM。它在整个极性范围内也显示出了出色的荧光特性，值得一个有前途的成像剂。通过结合体外光谱技术，计算机分子对接和诱导拟合对接（IFD），已经建立了HPFQ与HSA的结合机制。竞争性位点结合研究表明，否则HSA的阴离子受体半胱氨酸位点I会以审慎的亲和力（结合常数，Kb = 0.74×105 M-1）来培养中性HPFQ。时间分辨荧光研究表明，相对于HPFQ浓度增加，HSA平均辐射寿命显着降低，并提供了Forster共振能量转移（FRET）负责主要猝灭机制的证据，该过程由蛋白质主链中的微小结构变形陪伴着结构体。HPFQ在蛋白质基质内的Trp-214附近建立了自己，随后在“疏水氨基酸”中建立了自己。Trp-214占主导的环控环境经历了微极性的降低。HPFQ与HSA的较强结合触发了变构调节，从而导致蛋白质二级结构发生较小的变形。HSA的Sudlow位点I充分包含了可延展的面团等有​​利构象，从而为到达具有生物活性的HPFQ分子提供了空间。人们还认为，HPFQ可以通过影响HSA旋转异构体的相互转化来在HSA域中进行构象调节，这可能被证明是一个可启发性的领域，可以解码它们之间的优选相互作用。预期本文所述的并置的光谱学研究将增强设计以基于杂合鬼臼毒素的抗增殖临床剂的设计，以利用以HSA为中心的药物递送和给药系统进行有效的体内生物分布。