Pauli Exclusion by n→π* Interactions: Implications for Paleobiology.

Proteins have evolved to function in an aqueous environment. Collagen, which provides the bodily scaffold for animals, has a special need to retain its integrity. This need was addressed early on, as intact collagen has been detected in dinosaur fossils, even though peptide bonds have a half-life of only ∼500 years in a neutral aqueous solution. We sought to discover the physicochemical basis for this remarkable resistance to hydrolysis. Using experimental and computational methods, we found that a main-chain acyl group can be protected from hydrolysis by an O···C=O n→π* interaction with a neighboring acyl group. These interactions engage virtually every peptide bond in a collagen triple helix. This protection, which arises from the Pauli exclusion principle, could underlie the preservation of ancient collagen.