Polymeric Complements to the Alzheimer's Disease Biomarker 尾-Amyloid Isoforms A尾1鈥?0 and A尾1鈥?2 for Blood Serum Analysis under Denaturing Conditions

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• 作者：Javier L. Urraca ; Carla S. A. Aureliano ; Eric Schillinger ; Hermann Esselmann ; Jens Wiltfang ; B枚rje Sellergren
• 刊名：Journal of the American Chemical Society
• 出版年：2011
• 出版时间：June 22, 2011
• 年：2011
• 卷：133
• 期：24
• 页码：9220-9223
• 全文大小：746K
• 年卷期：v.133,no.24(June 22, 2011)
• ISSN：1520-5126

文摘

Treatment of Alzheimer's diesease (AD) is plagued by a lack of practical and reliable methods allowing early diagnosis of the disease. We here demonstrate that robust receptors prepared by molecular imprinting successfully address current limitations of biologically derived receptors in displaying affinity for hydrophobic peptide biomarkers for AD under denaturing conditions. C-terminal epitope-imprinted polymers showing enhanced binding affinity for A尾1鈥?2 were first identified from a 96-polymer combinatorial library. This information was then used to synthesize molecularly imprinted polymers for both of the 尾-amyloid (A尾) isoforms and a corresponding nonimprinted polymer. A solid-phase extraction method was developed to be compatible with sample loading under conditions of complete protein denaturation. This resulted in a method capable of quantitatively and selectively enriching a shorter C-terminal peptide corresponding to the sequences A尾33鈥?0 and A尾33鈥?2 as well as the full-length sequence A尾1鈥?0 and A尾1鈥?2 from a 4 M guanidinum chloride solution. Application of the method to serum allowed selective, high-recovery extraction of both biomarkers at spiking levels marginally higher than clinically relevant concentrations found in cerebrospinal fluid.