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

Proline derivatives bearing substituents at C gamma are valuable tools for biological and materials investigations. However, the stereochemistry at C gamma can produce undesired steric or stereoelectronic interactions. Here, we introduce gamma-azaproline (gamma-azPro), which lacks a stereogenic center at C gamma, 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 gamma-azPro is flexible. Incorporation of gamma-azPro into collagen model peptides (CMPs) produced pH-responsive triples helices and triple helices that can be easily functionalized.