Removal of intact ß2-microglobulin at neutral ph by using seed-conjugated polymer beads prepared with ß2-microglobulin-derived peptide (58-67).
Biotechnol Prog
; 27(2): 521-9, 2011.
Article
en En
| MEDLINE
| ID: mdl-21365783
ABSTRACT
Removal of ß2-microglobulin (ß2M) 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 ß2M removal strategy has been proposed by preparing seed-conjugated polymer beads and assimilating soluble ß2M to the fibrils on the surface at neutral pH. A novel peptide segment of ß2M 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 ß-sheet conformation. Because the peptide fibrils were successful to seed intact ß2M at neutral pH, the fibrils were immobilized on polymer beads of HiCore resins, and the resulting seed-conjugated beads were used to accrete intact ß2M in the form of fibrils elongated on the bead surface. Its efficiency of the ß2M removal was improved by placing the seed-immobilized beads in the middle of a continuous flow of the ß2M-containing solution as practiced in the blood circulation during the hemodialysis. Therefore, this ß2M removal system is suggested to exhibit high specificity, high binding capacity, and cost-effectiveness appropriate for eventual clinical application to remove ß2M from the blood of renal failure patients.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
/
Microglobulina beta-2
/
Amiloidosis
/
Enfermedades Renales
/
Microesferas
Tipo de estudio:
Etiology_studies
/
Evaluation_studies
Límite:
Humans
Idioma:
En
Revista:
Biotechnol Prog
Asunto de la revista:
BIOTECNOLOGIA
Año:
2011
Tipo del documento:
Article