Reduction in potency and reversal of left‐shifting activity of BW12C with the major and minor components of chicken hemoglobin

The effects of the left‐shifting, anti‐sickling compound BW12C (5‐(2‐formyl‐3‐hydroxyphenoxy)pentanoic acid) on the oxygen saturation curve of whole chicken blood and the isolated major (AII) and minor (AI) components of chicken hemoglobin have been studied. The results support the postulated major binding mode for BW12C to human hemoglobin of bridging between the α‐chain terminal amino groups in the oxy conformation with an important hydrophobic component contributed mainly by Pro 77α residues. In chicken AH (Pro 77 α → Ser) BW12C still left‐shifts at high concentrations but its potency is greatly reduced (at least 10‐fold). In chicken AI (Pro 77 α → Ser and Val 1 α → Met) BW12C is a right‐shifter with a potency comparable to that of 2,3‐diphosphoglycerate suggesting that binding at the β‐chain termini in the deoxy conformation is now dominant with α‐chain binding no longer significant.