Antivenom design based on amino acid sequence of complementarity determining regions (CDRs)

• Grant number: 16/07802-3
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2016
• End date: April 30, 2019
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Wilmar Dias da Silva
• Grantee: Marcos Jorge de Magalhaes Junior
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling, AP.CEPID

Abstract

Antibodies utilize complementarity-determining regions (CDRs) of their hypervariable regions to bind antigens. Their antigen binding amino acid sequence, located on VH and VL chains domains, has been copied and used as model to synthesize analogous peptides (5-9). Elimination of the support domains expressed on CH and CL chains abrogates their immunogenicity, but preserves antigen binding properties. Short peptides in solution assume a disordered conformation without a dominant folding pattern. To overpass this constraint, the synthetic peptides will be cycling and dimerized. Monospecific high affinity antivenom antibodies will be used as CDRs sources. Polypeptides using relevant protective monospecific single peptides will be constructed. The immunogenicity of the single or polypeptides will be further potentiated by polyacrilamide gel, BrCN-activated Sepharose or liposome coupling. Therefore, we intend obtain specific CDRs peptide sequences of two venom toxins, a phospholipase A2 found in Crotalus durissus terrificus venom and a hemorrhagic methalloprotease present in Bitis arietans venom.