γ-Azaproline Confers pH Responsiveness and Functionalizability on Collagen Triple Helices
Dr. Matthew R. Aronoff
Laboratory of Organic Chemistry, ETH Zürich, Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland
These authors contributed equally to this work.
Search for more papers by this authorJasmine Egli
Laboratory of Organic Chemistry, ETH Zürich, Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland
These authors contributed equally to this work.
Search for more papers by this authorMassimiliano Menichelli
Laboratory of Organic Chemistry, ETH Zürich, Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland
Search for more papers by this authorCorresponding Author
Prof. Helma Wennemers
Laboratory of Organic Chemistry, ETH Zürich, Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland
Search for more papers by this authorDr. Matthew R. Aronoff
Laboratory of Organic Chemistry, ETH Zürich, Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland
These authors contributed equally to this work.
Search for more papers by this authorJasmine Egli
Laboratory of Organic Chemistry, ETH Zürich, Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland
These authors contributed equally to this work.
Search for more papers by this authorMassimiliano Menichelli
Laboratory of Organic Chemistry, ETH Zürich, Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland
Search for more papers by this authorCorresponding Author
Prof. Helma Wennemers
Laboratory of Organic Chemistry, ETH Zürich, Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland
Search for more papers by this authorDedicated to Professor Ronald Raines on the occasion of a special birthday
Graphical Abstract
A chemical chameleon: γ-Azaproline was introduced as a pH-responsive and functionalizable amino acid with a conformation that can adapt to the environment. Incorporation into collagen triple helices showed its value as a tool to functionalize peptides and proteins and render them pH-responsive.
Abstract
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.
Supporting Information
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