Peptides can induce non IgE-mediated anaphylactoid reactions. These effects are triggered by the direct interaction of the peptide with mast cells that result in their degranulation and release of histamine and other inflammatory mediators.
The IRBM Peptide Chemistry Group in collaboration with the Merck &Co. team, recently published a paper describing on the optimization of a peptide lead based on the ProTx-II toxin mini-protein that target the NaV1.7 sodium channel receptor. The optimization effort resulted in the identification of new peptide candidates that minimize pseudo-allergic reactions mediated by acute mast cell degranulation (MCD).
The use of in vivo and PK/PD modeling approaches to screen and guide the optimization and chemical modifications of lead NaV1.7 peptides enabled the identification of substructures contributing to peptide mediated MCD and resulted in design of candidates with good in vivo tolerability at pharmacologically relevant, i.e. inhibitory, doses and exposures.