Removal of intact β2-microglobulin at neutral ph by using seed-conjugated polymer beads prepared with β2-microglobulin-derived peptide (58-67)

• Published in: Biotechnology progress Vol. 27; no. 2; pp. 521 - 529
• Main Authors: Kang, Sungsoo, Yang, Jee Eun, Kim, Jehoon, Ahn, Minkoo, Koo, Hee Jung, Kim, Mira, Lee, Yoon-Sik, Paik, Seung R.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.03.2011; Wiley
• Subjects: amyloid fibril formation; Amyloidosis - etiology; Amyloidosis - prevention & control; beta 2-Microglobulin - blood; beta 2-Microglobulin - isolation & purification; Biological and medical sciences; Biotechnology; dialysis-related amyloidosis; Fundamental and applied biological sciences. Psychology; Humans; Hydrogen-Ion Concentration; Kidney Diseases - complications; Kidney Diseases - therapy; kidney dysfunction; Methods; Microspheres; Peptide Fragments - therapeutic use; Renal Dialysis - adverse effects; seed-conjugated polymer bead; β2-microglobulin; β2-microglobulin removal; pH; Conjugated polymer; Peptides; β2-Microglobulin
• ISSN: 8756-7938; 1520-6033
• DOI: 10.1002/btpr.562

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. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011