Peptide inhibitors of sickle hemoglobin aggregation: effect of hydrophobicity.
Thirty-three peptides have been synthesized which have the ability to inhibit aggregation of sickle hemoglobin which occurs upon deoxygenation. Evidence is presented which indicates that the hydrophobicity of the side chains is the predominant factor. A linear correlation exists between the capacity of peptides to inhibit gelation and the additivity of the side-chain hydrophobic contributions. Small di- and tri-peptides are more responsive to changes in their nonpolar content than are larger oligopeptides whose antigelling activity is a slowly varying function of hydrophobicity. With few exceptions, charged substituent groups on the side chain do not appear to contribute to the inhibitory process. Thus, if hydrogen bonding or ionic interactions are involved with these residues, they appear to play only a secondary role in the molecular interactions responsible for inhibiting or delaying the deoxy-HbS gelation.
D002151:Calorimetry; D006451:Hemoglobin, Sickle; D006801:Humans; D009842:Oligopeptides; D011485:Protein Binding; D013329:Structure-Activity Relationship
D006451:Hemoglobin, Sickle; D009842:Oligopeptides