title: Removal of intact β2-microglobulin at neutral ph by using seed-conjugated polymer beads prepared with β2-microglobulin-derived peptide (58-67).
abstract: Removal of β2-microglobulin (β2M) from the blood of patients suffering from kidney dysfunction is crucial to protect those individuals from getting the diseased state of dialysis-related amyloidosis. By harnessing the nucleation-dependent fibrillation process of amyloidogenesis, a β2M removal strategy has been proposed by preparing seed-conjugated polymer beads and assimilating soluble β2M to the fibrils on the surface at neutral pH. A novel peptide segment of β2M ranging from residue 58 to residue 67 (Lys-Asp-Trp-Ser-Phe-Tyr-Leu-Leu-Tyr-Tyr), which was capable of being fibrillated at neutral pH was isolated. Charge interaction between the positive N-terminal lysine and the negative C-terminal α-carboxylic group was demonstrated to be critical for the molecular self-assembly leading to the peptide fibril formation by favoring β-sheet conformation. Because the peptide fibrils were successful to seed intact β2M at neutral pH, the fibrils were immobilized on polymer beads of HiCore resins, and the resulting seed-conjugated beads were used to accrete intact β2M in the form of fibrils elongated on the bead surface. Its efficiency of the β2M removal was improved by placing the seed-immobilized beads in the middle of a continuous flow of the β2M-containing solution as practiced in the blood circulation during the hemodialysis. Therefore, this β2M removal system is suggested to exhibit high specificity, high binding capacity, and cost-effectiveness appropriate for eventual clinical application to remove β2M from the blood of renal failure patients.
authors.affiliation: School of Chemical and Biological Engineering, Seoul National University, Seoul 151-744, Korea.
authors.forename: Sungsoo
authors.initials: S
authors.lastname: Kang
authors.forename: Jee Eun
authors.initials: JE
authors.lastname: Yang
authors.forename: Jehoon
authors.initials: J
authors.lastname: Kim
authors.forename: Minkoo
authors.initials: M
authors.lastname: Ahn
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Koo
authors.forename: Mira
authors.initials: M
authors.lastname: Kim
authors.forename: Yoon-Sik
authors.initials: YS
authors.lastname: Lee
authors.forename: Seung R
authors.initials: SR
authors.lastname: Paik
mesh_terms: D000686:Amyloidosis / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007674:Kidney Diseases / Q000150:complications* / Q000628:therapy; D008722:Methods; D008863:Microspheres; D010446:Peptide Fragments / Q000627:therapeutic use; D006435:Renal Dialysis / Q000009:adverse effects; D001613:beta 2-Microglobulin / Q000097:blood / Q000302:isolation & purification*
chemical_list: D010446:Peptide Fragments; D001613:beta 2-Microglobulin