Pauli Exclusion\nby n→π* Interactions:\nImplications for Paleobiology

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