Allosteric regulation of conformational enantiomerism. Bilirubin

(4Z,15Z)-Bilirubin IXα, the cytotoxic yellow tetrapyrrole pigment of jaundice, readily adopts either of two interconverting, enantiomeric conformations, which are stabilized through complementary intramolecular hydrogen bonding between the pyrrole and lactam N-H and C=O residues of one dipyrrinone moiety and the CO 2 H group of propionic acid side chains on the second dipyrrinone. One conformational enantiomer can be destabilized relative to the other through allosteric action by judicious placement of methyl groups in the propionic acid side chains. Thus, insertion of a methyl group at the pro-R site on the α-carbon of the propionic acid destabilizes the M-chirality intramolecularly hydrogen-bonded conformational enantiomer by introducing a severe nonbonded CH 3 |CH 3 steric interaction with a pyrrole methyl substituent