Novel biomimetic affinity ligands for human tissue plasminogen activator.
Dyes-based biomimetic affinity chromatography has been used to purify therapeutically useful proteins. In order to design novel biomimetic affinity ligands for purification of tissue-type plasminogen activator (t-PA), small molecular fragments were achieved to fit in S3/4 binding site of t-PA by structure-based ligand design method (InsightII/Ludi). Three biomimetic affinity ligands A, B, and C were then designed, synthesized, and proved to bind the target protein (t-PA), exceeding the binding capacity of the commercial p-amino benzamidine affinity matrix. The designed affinity matrix A showed high efficiency to purify sc-tpa from the crude samples with 18-fold of purification.
Wu
Fang
F
Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland. fangwu@bioc.unizh.ch
Yu
Jing
J
Li
Rongxiu
R
D001550:Benzamidines / Q000138:chemical synthesis / Q000737:chemistry*; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry*; D002846:Chromatography, Affinity / Q000379:methods*; D006801:Humans; D008024:Ligands; D010959:Tissue Plasminogen Activator / Q000737:chemistry / Q000302:isolation & purification*; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry*
D001550:Benzamidines; D008024:Ligands; D014227:Triazines; D010959:Tissue Plasminogen Activator