Inhibition of deoxyhemoglobin S polymerization by biaromatic peptides found to associate with the hemoglobin molecule at a preferred site.

Association of three succinylated biaromatic peptides with deoxyhemoglobin has been measured. These peptides composed of indolyl or phenyl rings were found to have delta G values for their binding to deoxyhemoglobin between -2.9 and -3.4 kcal/mol at 23 degrees C. Binding experiments among these peptides demonstrate one preferred site, one of strongest binding of the peptide to the Hb molecule, as well as the existence of one or more weaker binding sites. Both aromatic side chains and at least one of the terminal carboxyl groups of the succinylated peptides are involved in the interactions with the hemoglobin (Hb) side chains at the preferred binding site. The latter also was found to be capable of binding monocyclic moieties of sufficient hydrophobicity, i.e., indolyl ring compounds. Increases in deoxyhemoglobin S (deoxy-HbS) solubilities in the presence of these three biaromatic peptides show a strong correlation between the values of their dissociation constants and their ability to destabilize deoxy-HbS aggregation. The symmetric site to which the peptides bind must be located at or near a contact site needed to stabilize the deoxy-HbS polymer.