title: Differential interactions and structural stability of chitosan oligomers with human serum albumin and α-1-glycoprotein.
abstract: Chitosan is a naturally occurring deacetylated derivative of chitin with versatile biological activities. Here, we studied the interaction of chitosan oligomers with low degree of polymerization such as chitosan monomer (CM), chitosan dimer (CD), and chitosan trimer (CT) with human serum albumin (HSA) a major blood carrier protein and α-1-glycoprotein (AGP). Since, HSA and AGP are the two important plasma proteins that determine the drug disposition and affect the fate of distribution of drugs. Fluorescence emission spectra indicated that CM, CD, and CT had binding constants of KCM = 6.2 ± .01 × 10(5) M(-1), KCD = 5.0 ± .01 × 10(4) M(-1), and KCT = 1.6 ± .01 × 10(6) M(-1), respectively, suggesting strong binding with HSA. However, binding of chitooligomers with AGP was insignificant. Thermodynamic and molecular docking analysis indicated that hydrogen bonds and also hydrophobic interaction played an important role in stabilizing the HSA-chitooligomer complexes with free energies of -7.87, -6.35, and -8.4 Kcal/mol for CM, CD, and CT, respectively. Further, circular dichroism studies indicated a minor unfolding of HSA secondary structure, upon interaction with chitooligomers, which are supported with fluctuations of root mean square deviation (RMSD) and radius of gyration (Rg) of HSA. Docking analysis revealed that all three chitooligomers were bound to HSA within subdomain IIA (Site I). In addition, RMSD and Rg analysis depicted that HSA-chitooligomer complexes stabilized at around 4.5 ns. These results suggest that HSA might serve as a carrier in delivering chitooligomers to target tissues than AGP which has pharmacological importance.
authors.affiliation: a Department of Biochemistry , School of Life Sciences, University of Hyderabad , Hyderabad 500046 , India.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Gokara
authors.forename: Geetha Bai
authors.initials: GB
authors.lastname: Kimavath
authors.forename: Appa Rao
authors.initials: AR
authors.lastname: Podile
authors.forename: Rajagopal
authors.initials: R
authors.lastname: Subramanyam
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D001667:Binding, Competitive; D048271:Chitosan / Q000737:chemistry* / Q000378:metabolism; D019281:Dimerization; D006801:Humans; D006860:Hydrogen Bonding; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D009961:Orosomucoid / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012709:Serum Albumin / Q000737:chemistry* / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics
chemical_list: D009961:Orosomucoid; D012709:Serum Albumin; D048271:Chitosan
keywords: chitooligomers; drug binding; fluorescence quenching; human serum albumin; molecular dynamics simulation; α-glycoprotein