In linear polypeptides, inversion of amino acid chirality (all-l to all-d) achieves a mirroring of side chain positions and interactions in conformational space. A similar mirroring of side chain positions is independently achieved by a reversal of the direction of the peptide backbone (retro modification). Thus, while an all-d chain could be expected to adopt a perfect ‘mirror image’ of the three-dimensional structure of its parent all-l protein, the retro-all-l chain could be expected to adopt a topological equivalent of such a mirror image, through the symmetry transformations of side chain interactions. These notions, supported by sequence analyses, modelling studies, and evidence relating to the activity of ‘retro-inverso’ peptides, are extended towards the proposal, that the backbone reversed chain of a large globular protein might recognize the chiral opposite of the parent protein's substrate(s).
