Practical N-to-C peptide synthesis with minimal protecting groups.

Accessible drug modalities have continued to increase in number in recent years. Peptides play a central role as pharmaceuticals and biomaterials in these new drug modalities. Although traditional peptide synthesis using chain-elongation from C- to N-terminus is reliable, it produces large quantities of chemical waste derived from protecting groups and condensation reagents, which place a heavy burden on the environment. Here we report an alternative N-to-C elongation strategy utilizing catalytic peptide thioacid formation and oxidative peptide bond formation with main chain-unprotected amino acids under aerobic conditions. This method is applicable to both iterative peptide couplings and convergent fragment couplings without requiring elaborate condensation reagents and protecting group manipulations. A recyclable N-hydroxy pyridone additive effectively suppresses epimerization at the elongating chain. We demonstrate the practicality of this method by showcasing a straightforward synthesis of the nonapeptide DSIP. This method further opens the door to clean and atom-efficient peptide synthesis.

Long-term outcomes of oral immunotherapy for anaphylactic egg allergy in children.

Background: Studies of long-term oral immunotherapy (OIT) in children with anaphylactic egg allergy are limited. Objective: Our aim was to investigate the long-term outcomes of OIT for anaphylactic egg allergy. Methods: The participants included children (aged ≥ 5 years) with a history of anaphylaxis in response to eggs and objective reactions to oral food challenge (OFC) with 250 mg of egg protein. In the OIT group, the home starting dose of egg protein set during 5 days of hospitalization was ingested once daily and gradually increased to 1000 mg. Over the next year, participants temporarily discontinued OIT for 2 weeks and underwent OFC with 3100 mg of egg protein annually until they passed. The historical control group comprised patients who did not receive OIT and repeated OFCs annually. Results: In the OIT group (n = 20), the baseline median egg white- and ovomucoid-specific IgE levels were 45.5 and 38.5 kUA/L, respectively. The rate of passing OFC with 3100 mg of egg protein gradually increased in the OIT group, with rates of 20% at 1 year, 35% at 2 years, and 55% at 3 years, which were significantly higher than the rates in the historical control group at 3 years (5% [P < .001]). In the OIT group, 5 anaphylaxis events (0.04%) occurred at home, and 1 participant required intramuscular adrenaline. Furthermore, egg white- and ovomucoid-specific IgE levels decreased significantly after 3 years in both groups, whereas in the OIT group, these specific IgG and IgG4 levels increased significantly after a year. Conclusion: Long-term OIT accelerated immunologic changes and enabled ingestion of 3100 mg of egg protein in half of the participants with anaphylactic egg allergy.

A catalytic one-step synthesis of peptide thioacids: the synthesis of leuprorelin via iterative peptide-fragment coupling reactions.

A catalytic one-step synthesis of peptide thioacids was developed. The oxygen-sulfur atom exchange reaction converted the carboxy group at the C-terminus of the peptides into a thiocarboxy group with suppressed epimerization. This method was successfully applied to the synthesis of the peptide drug leuprorelin via an iterative fragment-coupling protocol.