On the Synthesis of Conformationally Modified Peptides through Isonitrile Chemistry: Implications for Dealing with Polypeptide Aggregation

A method for introducing a dimethyleneoxy constraint joining the N atoms of two consecutive amino acids in the context of a polypeptide has been developed. This constraint can profoundly affect the tendency of a polypeptide to suffer aggregation and desolubilization, and it can be readily removed under mild conditions.