Removal of Intact β2-Microglobulin at Neutral pH by Using Seed-Conjugated Polymer Beads Prepared with β2-MicroglobuIin-Derived Peptide (58-67)

摘要

Removal of β-microglobulin (β2M) from the blood of patients suffering from kidney dysfunction is crucial to protect those individuals from getting the diseased state of dialysisrelated amyloidosis. By harnessing the nucleation-dependent fibrillation process of amyloidogenesis, a fS2M 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 βM-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.