title: Concentration-dependent antagonistic persuasion of SDS and naphthalene derivatives on the fibrillation of stem bromelain.
abstract: Sodium dodecyl sulfate, a biological membrane mimetic, can be used to study the conversion of globular proteins into amyloid fibrils in vitro. Using multiple approaches, the effect of SDS was examined on stem bromelain (SB), a widely recognized therapeutic protein. SB is known to exist as a partially folded intermediate at pH 2.0, situation also encountered in the gastrointestinal tract (its site of absorption). In the presence of sub-micellar SDS concentration (500-1000 μM), this intermediate was found to exhibit great propensity to form large-sized β-sheeted aggregates with fibrillar morphology, the hall marks of amyloid structure. We also observed inhibition of fibrillation by two naphthalene-based compounds, ANS and bis-ANS. While bis-ANS significantly inhibited fibril formation at 50 μM, ANS did so at relatively higher concentration (400 μM). Alcohols, but not salts, were found to weaken the inhibitory action of these compounds suggesting the possible involvement of hydrophobic interactions in their binding to protein. Besides, isothermal titration calorimetry and molecular docking studies suggested that inhibition of fibrillation by these naphthalene derivatives is mediated not just through hydrophobic forces, but also by disruption of π-π interactions between the aromatic residues together with the inter-polypeptide chain repulsion among negatively charged ANS/bis-ANS bound SB.
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Atiyatul
authors.initials: A
authors.lastname: Qadeer
authors.forename: Ejaz
authors.initials: E
authors.lastname: Ahmad
authors.forename: Masihuz
authors.initials: M
authors.lastname: Zaman
authors.forename: Mohd Wasif
authors.initials: MW
authors.lastname: Khan
authors.forename: Javed Masood
authors.initials: JM
authors.lastname: Khan
authors.forename: Gulam
authors.initials: G
authors.lastname: Rabbani
authors.forename: Khaja Faisal
authors.initials: KF
authors.lastname: Tarique
authors.forename: Gaurav
authors.initials: G
authors.lastname: Sharma
authors.forename: Samudrala
authors.initials: S
authors.lastname: Gourinath
authors.forename: Sajid
authors.initials: S
authors.lastname: Nadeem
authors.forename: Gamal
authors.initials: G
authors.lastname: Badr
authors.forename: Rizwan Hasan
authors.initials: RH
authors.lastname: Khan
mesh_terms: D000438:Alcohols / Q000494:pharmacology; D001963:Bromelains / Q000737:chemistry* / Q000378:metabolism; D002021:Buffers; D004305:Dose-Response Relationship, Drug; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008823:Micelles; D062105:Molecular Docking Simulation; D009281:Naphthalenes / Q000737:chemistry* / Q000494:pharmacology*; D055503:Protein Multimerization / Q000187:drug effects*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012967:Sodium Dodecyl Sulfate / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D000438:Alcohols; D002021:Buffers; D008823:Micelles; D009281:Naphthalenes; C031721:naphthalene; D012967:Sodium Dodecyl Sulfate; D001963:Bromelains; C091760:stem bromelain
keywords: ANS; Amyloid inhibition; Bis-ANS; SDS; Stem bromelain; π–π Interactions