γ-Azaproline Confers pH Responsiveness and Functionalizability on Collagen Triple Helices.

Proline derivatives bearing substituents at Cγ are valuable tools for biological and materials investigations. However, the stereochemistry at Cγ can produce undesired steric or stereoelectronic interactions. Here, we introduce γ-azaproline (γ-azPro), which lacks a stereogenic center at Cγ, as a pH-responsive and functionalizable proline analogue that can adapt to its environment. Conformational analyses by NMR spectroscopy and DFT calculations revealed that the imidazolidine ring of γ-azPro is flexible. Incorporation of γ-azPro into collagen model peptides (CMPs) produced pH-responsive triples helices and triple helices that can be easily functionalized.