The downfall of the overall cyclol model generally led to a rejection of its elements; one notable exception was J. D. Bernal's short-lived acceptance of the Langmuir-Wrinch hypothesis that protein folding is driven by hydrophobic association. Nevertheless, cyclol bonds were identified in small, naturally occurring cyclic peptides in the 1950s.
Clarification of the modern terminology is appropriate. The classic cyclol reaction is the addition of the NH amine of a peptide group to the C=O carbonyl group of another; the resulting compound is now called an azacyclol. By analogy, an oxacyclol is formed when an OH hydroxyl group is added to a peptidyl carbonyl group. Likewise, a thiacyclol is formed by adding an SH thiol moiety to a peptidyl carbonyl group.
The oxacyclol alkaloid ergotamine from the fungus Claviceps purpurea was the first identified cyclol. The cyclic depsipeptide serratamolide is also formed by an oxacyclol reaction. Chemically analogous cyclic thiacyclols have also been obtained. Classic azacyclols have been observed in small molecules and tripeptides. Peptides are naturally produced from the reversion of azacylols, a key prediction of the cyclol model. Hundreds of cyclol molecules have now been identified, despite Linus Pauling's calculation that such molecules should not exist because of their unfavorably high energy.
After a long hiatus during which she worked mainly on the mathematics of X-ray crystallography, Wrinch responded to these discoveries with renewed enthusiasm for the cyclol model and its relevance in biochemistry. She also published two books describing the cyclol theory and small peptides in general.