Use of surface plasmon resonance to study the elongation kinetics and the binding properties of the highly amyloidogenic Aβ_1–42 peptide, synthesized by depsi-peptide technique

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• 作者：Matteo Stravalaci¹ ; ^a ; Marten Beeg¹ ; ^a ; Mario Salmona^a ; Marco Gobbi ; ^a ; ^{Marco.Gobbi@marionegri.it}
• 关键词：Amyloid-β ; peptides ; Depsi-peptides ; Polymerization kinetics ; Fibril elongation ; Surface plasmon resonance
• 刊名：Biosensors and Bioelectronics
• 出版年：2011
• 出版时间：15 January 2011
• 年：2011
• 卷：26
• 期：5
• 页码：2772-2775
• 全文大小：326 K

文摘

A wide variety of human diseases are associated with the formation of highly organized protein aggregates termed amyloid fibrils, whose growth (elongation) is due to the assembly of the basic molecular units (monomers) in a sequential polymerization process.

Surface plasmon resonance (SPR) technology has been proposed as a powerful approach to study in detail the fibril elongation of some amyloidogenic peptides. In particular, the injection of monomers over immobilized fibrils allows to follow in real time, and on a very short time-scale, the kinetics of fibril growth. In the present study we confirmed and extended this application of SPR to Aβ_1–42, hampered till now by the very pronounced aggregation propensity of this peptide, involved in Alzheimer disease. We took advantage of a new synthetic strategy (“depsi-peptide” technique) which allows to obtain reliable seed-free solutions (monomers) as well as fibrils of Aβ_1–42. SPR data were consistent with a “dock-and-lock” mechanism underlying Aβ_1–42 elongation process. The setup of an assay monitoring the elongation kinetics is very useful for investigating potential anti-amyloidogenic compounds. Moreover, the possibility to reliably immobilize both Aβ_1–42 monomers and fibrils allows to measure the binding affinities of putative ligands for these different species. The approach applied here to Aβ_1–42 might well be also applied to the study of other fibrillogenic peptides/proteins or to the study of polymerization reactions in general.