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Mech Ageing Dev. 2020 Jan;185:111188. doi: 10.1016/j.mad.2019.111188. Epub 2019 Nov 26.

Catalytic antibody (catabody) platform for age-associated amyloid disease: From Heisenberg's uncertainty principle to the verge of medical interventions.

Author information

1
6218 Copin Lake Lane, Missouri City, TX, 77459, USA.
2
6218 Copin Lake Lane, Missouri City, TX, 77459, USA. Electronic address: sudhirpaul@covalentbioscience.com.

Abstract

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.

KEYWORDS:

Amyloid disease; Catalytic antibodies; Electrophilic vaccines; First-line anti-aging defense; Infectious disease

PMID:
31783036
PMCID:
PMC6938548
[Available on 2021-01-01]
DOI:
10.1016/j.mad.2019.111188

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