Quantum mechanics-based design of useful catalytic antibodies (catabodies) failed because of the uncertain structure of the dynamic catalyst-substrate complex. The Catabody Platform emerged from discovery of beneficial germline gene catabodies that hydrolyzed self-proteins by transient covalent pairing of the strong catabody nucleophile with a weak target protein electrophile. Catabodies have evolved by Darwinian natural selection for protection against misfolded self-proteins that threatened survival by causing amyloid disease. Ancient antibody scaffolds upregulate the catalytic activity of the antibody variable (V) domains. Healthy humans universally produce beneficial catabodies specific for at least 3 misfolded self-proteins, transthyretin, amyloid β peptide and tau protein. Catabody are superior to ordinary antibodies because of catalyst reuse for thousands of target destruction cycles with little or no risk of causing inflammation, a must for non-toxic removal of abundant targets such as amyloids. Library mining with electrophilic target analogs (ETAs) isolates therapy-grade catabodies (fast, specific). Ex vivo- and in vivo-verified catabodies specific for the misfolded protein are available to dissolve brain, cardiac and vertebral amyloids. Immunization with ETAs overcomes important ordinary vaccine limitations (no catabody induction, poor immunogenicity of key target epitopes). We conceive electrophilic longevity vaccines that can induce catabody synthesis for long-lasting protection against amyloid disease.

中文翻译：

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年龄相关性淀粉样变性疾病的催化抗体（催化抗体）平台：从海森堡的不确定性原理到医疗干预的边缘。

由于动态催化剂-底物复合物的结构不确定，基于量子力学的有用催化抗体（催化体）设计失败。Catabody平台源于有益种系基因代谢物的发现，该代谢物通过强催化体亲核体与弱目标蛋白亲电体的瞬时共价配对来水解自身蛋白。达尔文自然选择已经进化出了代谢物，用于保护自身蛋白质折叠错误，该蛋白质折叠导致的淀粉样蛋白病威胁生存。古老的抗体支架上调抗体可变（V）域的催化活性。健康的人类普遍产生对至少3种错误折叠的自身蛋白，运甲状腺素蛋白，淀粉样β肽和tau蛋白特异的有益代谢。Catabody优于普通抗体，因为催化剂可重复使用数千个目标破坏循环，几乎没有或根本没有引起炎症的风险，而无毒去除大量目标（如淀粉样蛋白）则是必不可少的。使用亲电子靶标类似物（ETA）进行文库挖掘可分离出治疗级别的代谢物（快速，特异）。对错误折叠的蛋白质特异的离体和体内验证的代谢物可用于溶解脑，心脏和椎骨淀粉样蛋白。用ETA免疫可克服重要的普通疫苗局限性（无催化抗体诱导作用，关键目标表位的免疫原性差）。我们构想了可以诱导catabody合成以长期抵抗淀粉样变性疾病的亲电长寿疫苗。无毒去除大量目标（如淀粉样蛋白）的必需品。使用亲电子靶标类似物（ETA）进行文库挖掘可以分离出治疗级别的代谢物（快速，特异）。特异于错误折叠的蛋白质的离体和体内验证的代谢物可用于溶解脑，心脏和椎骨淀粉样蛋白。用ETA免疫可克服重要的普通疫苗局限性（无催化抗体诱导作用，关键目标表位的免疫原性差）。我们构想了可以诱导catabody合成以长期抵抗淀粉样变性疾病的亲电长寿疫苗。无毒去除大量目标（如淀粉样蛋白）的必需品。使用亲电子靶标类似物（ETA）进行文库挖掘可分离出治疗级别的代谢物（快速，特异）。对错误折叠的蛋白质特异的离体和体内验证的代谢物可用于溶解脑，心脏和椎骨淀粉样蛋白。用ETA免疫可克服重要的普通疫苗局限性（无催化抗体诱导作用，关键目标表位的免疫原性差）。我们构思了可以诱导catabody合成以长期保护淀粉样变性疾病的亲电长寿疫苗。心脏和椎体淀粉样蛋白。用ETA免疫可克服重要的普通疫苗局限性（无催化抗体诱导作用，关键目标表位的免疫原性差）。我们构想了可以诱导catabody合成以长期抵抗淀粉样变性疾病的亲电长寿疫苗。心脏和椎体淀粉样蛋白。用ETA免疫可克服重要的普通疫苗局限性（无催化抗体诱导作用，关键目标表位的免疫原性差）。我们构想了可以诱导catabody合成以长期抵抗淀粉样变性疾病的亲电长寿疫苗。