Preparation of artificial receptors for beta-amyloid protein by hierarchical imprinting techniques.

阿尔茨海默S病(AD)是人类最常见的痴呆症。最近的研究表明，大脑淀粉样斑块的沉积是疾病过程的中心，淀粉样沉积主要由淀粉样前体蛋白(APP)的蛋白水解性裂解而产生的38-43个氨基酸的β-淀粉样蛋白(A？)聚集体组成。理论上，较大的多肽(42-43个氨基酸残基)对聚集更有效，从而导致斑块形成和神经元死亡。因此，人们对几种淀粉样蛋白的分离和分化越来越感兴趣。到目前为止，由于选择性不足、成本高或生产困难，传统的分离技术或免疫分析在这方面的前景不大。将利用先前开发的表面印迹技术(参见DFG SE 777/5-1)来制造人工多肽受体，该技术使用粗固相肽合成产品(短序列的~lt；5个氨基酸)作为模板，在介孔聚合物珠中生成表位印迹表面。这些珠子将被靶向展示对目标肽的N-末端或C-末端序列的识别。整个多肽，包括不同的末端(40、41、42、43个残基)，将作为靶标，并评估所得到的珠子从脑脊液(CSF)或血浆中选择性地提取和丰富A？变体的能力，以用于分析(诊断)或治疗(血液治疗)目的。

Alzheimer s disease (AD) is the most common form of dementia in humans. Recent researchsuggests that the deposition of cerebral amyloid plaques is central to the disease process.Amyloid deposits mainly comprise aggregates of ß-amyloid (Aß), a 38-43 amino acid peptidederived by proteolytic cleavage of the amyloid precursor protein (APP). The larger peptides(42-43 amino acid residues) are theorised to be more potent towards aggregation and, thus,plaque formation and neuronal death. Therefore, there is an increased interest in theseparation and differentiation between the several amyloid forms. Conventional separationtechniques or immunoassays have so far shown less promise for such purposes due toinsufficient selectivity, high cost or difficulties in production. Artificial receptors for Aß-peptideswill be manufactured utilising a previously developed surface imprinting technique(see DFG SE 777/5-1), This uses crude solid phase peptide synthesis products (shortsequences of < 5 amino acids) as templates to generate epitope-imprinted surfaces inmesoporous polymer beads. The beads will be targeted to exhibit recognition of the N- or C-terminalsequences of the target peptide. The entire peptide, including the varying terminals(40, 41, 42, 43 residues), will be targeted and the resulting beads assessed for their ability toselectively extract and enrich the Aß variants from cerebrospinal fluid (CSF) or blood plasmafor analytical (diagnostic) or therapeutic (blood treatment) purposes.