Late-stage peptide and protein modifications through phospha-Michael addition reaction.

We developed a late-stage modification strategy by a phospha-Michael addition reaction between various functional phosphines and unprotected dehydroalanine (Dha) peptides and proteins under mild conditions. This strategy was applied to generate a staple peptide to enhance its cell membrane penetrability, and it was also able to regulate alpha-synuclein aggregation properties and morphological characteristics with the addition of different charges.