BIOM30002 Lecture Notes - Lecture 34: Immunosuppressive Drug, Histidine, Protein Structure
Document Summary
These assays have been used to identify key amino acid residues and oligomeric structure involved in neurotoxicity of amyloid beta peptide: Oligomeric forms of amyloid beta peptide are neurotoxic. Mutation of histidine residues (his6, his13 and his14 within abeta sequence) affect cu binding and reduce neurotoxicity of peptide (reduced aggregation and free radical generation) Mutation of tyr10 also reduces toxicity tyrosine is important in di-tyrosine cross- linking between peptides to promote oligomer formation and toxicity. All of these come from growing cells in culture and looking at their viability in different forms. Drugs compounds may be designed to target and inhibit an enzyme (antagonist/inhibitor) (eg calcineurin inhibitor). Drugs/molecules may also activate enzymes (growth factors and peptides derived from growth factors). May design drug based on protein structure (identified through crystallography etc) Cross blood brain barrier (this is actually a big challenge) But this approach has had many failures, perhaps better to look at other ways.
