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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/HBA_HUMAN HBA_HUMAN]] Involved in oxygen transport from the lung to the various peripheral tissues. [[http://www.uniprot.org/uniprot/HBB_HUMAN HBB_HUMAN]] Involved in oxygen transport from the lung to the various peripheral tissues.<ref>PMID:16904236</ref> LVV-hemorphin-7 potentiates the activity of bradykinin, causing a decrease in blood pressure.<ref>PMID:16904236</ref> | [[http://www.uniprot.org/uniprot/HBA_HUMAN HBA_HUMAN]] Involved in oxygen transport from the lung to the various peripheral tissues. [[http://www.uniprot.org/uniprot/HBB_HUMAN HBB_HUMAN]] Involved in oxygen transport from the lung to the various peripheral tissues.<ref>PMID:16904236</ref> LVV-hemorphin-7 potentiates the activity of bradykinin, causing a decrease in blood pressure.<ref>PMID:16904236</ref> | ||
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== Publication Abstract from PubMed == | |||
Aromatic aldehydes and ethacrynic acid (ECA) exhibit antipolymerization properties that are beneficial for sickle cell disease therapy. Based on the ECA pharmacophore and its atomic interaction with hemoglobin, we designed and synthesized several compounds - designated as KAUS (imidazolylacryloyl derivatives) - that we hypothesized would bind covalently to betaCys93 of hemoglobin and inhibit sickling. The compounds surprisingly showed weak allosteric and antisickling properties. X-ray studies of hemoglobin in complex with representative KAUS compounds revealed an unanticipated mode of Michael addition between the beta-unsaturated carbon and the N-terminal alphaVal1 nitrogen at the alpha-cleft of hemoglobin, with no observable interaction with betaCys93. Interestingly, the compounds exhibited almost no reactivity with the free amino acids, l-Val, l-His and l-Lys, but showed some reactivity with both glutathione and l-Cys. Our findings provide a molecular level explanation for the compounds biological activities and an important framework for targeted modifications that would yield novel potent antisickling agents. | |||
Identification of a novel class of covalent modifiers of hemoglobin as potential antisickling agents.,Omar AM, Mahran MA, Ghatge MS, Chowdhury N, Bamane FH, El-Araby ME, Abdulmalik O, Safo MK Org Biomol Chem. 2015 May 27;13(22):6353-70. doi: 10.1039/c5ob00367a. PMID:25974708<ref>PMID:25974708</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
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== References == | == References == | ||
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