SPECIES DIFFERENCES IN THE BINDING OF COMPOUNDS DESIGNED TO FIT A SITE OF KNOWN STRUCTURE IN ADULT HUMAN HAEMOGLOBIN

Abstract

1 Oxygen dissociation curves are reported for human haemoglobins A₁, F_II, F^I, A_1C and Raleigh ifil valine → acetylalanine) and for horse haemoglobin in the absence and presence of 2,3-diphos-phoglycerate (DPG), or 4,4′-diformyl-2-bibenzyl oxyacetic acid, or the bisulphite addition compound of the latter. 2 These haemoglobins were selected because their amino acid sequences are different at the DPG receptor site of human adult deoxyhaemoglobin. 3 The size of the shifts of the dissociation curves are in the sequence expected from the postulated numbers of interactions made by each compound with each haemoglobin type, based on the assumption of a common receptor site for the three compounds. 4 Multiple linear regression analysis shows that the free energies of interaction of the compounds with the haemoglobins may be predicted, to a first approximation, by summing the number of ionic and covalent bonds predicted for each effector-receptor combination, a reversible covalent bond contributing about twice as much energy (-6.78 kJmol⁻¹) as an ionic interaction (−3.14 kJmol⁻¹).