Specific chemical modifications in the beta-cleft site of hemoglobin. Potential anti-sickling agents with hybrid functionalities.
Ester and aldehyde groups have been combined to produce molecules with hybrid functionalities that might be effective in modifying hemoglobin. In this series of compounds, the reagents that carry the combination of an anionic charge and an aldehyde as binding groups show a strong preference for the beta-cleft region of the protein and produce selective modification therein. 5-Formylaspirin and related oxalyl, malonyl, and fumaryl monoaldehyde monoester derivatives form a new class of substances for which modification of hemoglobin is very substantial and is inhibited by inositol hexaphosphate.
D000215:Acylation; D000328:Adult; D000447:Aldehydes / Q000494:pharmacology*; D000986:Antisickling Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001665:Binding Sites; D006441:Hemoglobin A / Q000378:metabolism*; D006451:Hemoglobin, Sickle / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D000447:Aldehydes; D000986:Antisickling Agents; D006451:Hemoglobin, Sickle; D006441:Hemoglobin A