Switching of Trp-214 intrinsic rotamer population in human serum albumin: An insight into the aftermath of embracing therapeutic bioorganic luminophore azapodophyllotoxin into sudlow site I
| Autor: | Naina Sehra, Sujit Kumar Ghosh, Ajay Kumar, Soham Mukherjee, Kapil Ganorkar |
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| Rok vydání: | 2018 |
| Předmět: |
Population
Allosteric regulation Serum Albumin Human 01 natural sciences Biochemistry Protein structure Furocoumarins Drug Discovery medicine Humans education Molecular Biology Protein secondary structure education.field_of_study Quenching (fluorescence) Molecular Structure 010405 organic chemistry Chemistry Organic Chemistry Tryptophan Human serum albumin 0104 chemical sciences Molecular Docking Simulation 010404 medicinal & biomolecular chemistry Förster resonance energy transfer Biophysics Hydrophobic and Hydrophilic Interactions Fluorescence anisotropy medicine.drug |
| Zdroj: | Bioorganic chemistry. 84 |
| ISSN: | 1090-2120 |
| Popis: | 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 K b = 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. |
| Databáze: | OpenAIRE |
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