5urc: Difference between revisions

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 ==Design, Synthesis, Functional and Biological Evaluation of Ether and Ester Derivatives of the Antisickling Agent 5-HMF for the Treatment of Sickle Cell Disease==
-<StructureSection load='5urc' size='340' side='right' caption='[[5urc]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
+<StructureSection load='5urc' size='340' side='right'caption='[[5urc]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[5urc]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5URC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5URC FirstGlance]. <br>
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 == 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>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Candidate drugs to counter intracellular polymerization of deoxygenated sickle hemoglobin (Hb S) continue to represent a promising approach to mitigating the primary cause of the pathophysiology associated with sickle cell disease (SCD). One such compound is the naturally occurring antisickling agent, 5-hydroxymethyl-2-furfural (5-HMF), which has been studied in the clinic for the treatment of SCD. As part of our efforts to develop novel efficacious drugs with improved pharmacologic properties, we structurally modified 5-HMF into 12 ether and ester derivatives. The choice of 5-HMF as a pharmacophore was influenced by a combination of its demonstrated attractive hemoglobin modifying and antisickling properties, well-known safety profiles, and its reported nontoxic major metabolites. The derivatives were investigated for their time- and/or dose-dependent effects on important antisickling parameters, such as modification of hemoglobin, corresponding changes in oxygen affinity, and inhibition of red blood cell sickling. The novel test compounds bound and modified Hb and concomitantly increased the protein affinity for oxygen. Five of the derivatives exhibited 1.5- to 4.0-fold higher antisickling effects than 5-HMF. The binding mode of the compounds with Hb was confirmed by X-ray crystallography and, in part, helps explain their observed biochemical properties. Our findings, in addition to the potential therapeutic application, provide valuable insights and potential guidance for further modifications of these (and similar) compounds to enhance their pharmacologic properties.
+Design, Synthesis, and Biological Evaluation of Ester and Ether Derivatives of Antisickling Agent 5-HMF for the Treatment of Sickle Cell Disease.,Xu GG, Pagare PP, Ghatge MS, Safo RP, Gazi A, Chen Q, David T, Alabbas AB, Musayev FN, Venitz J, Zhang Y, Safo MK, Abdulmalik O Mol Pharm. 2017 Oct 2;14(10):3499-3511. doi: 10.1021/acs.molpharmaceut.7b00553., Epub 2017 Sep 13. PMID:28858508<ref>PMID:28858508</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 5urc" style="background-color:#fffaf0;"></div>
 ==See Also==
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 </StructureSection>
 [[Category: Homo sapiens]]
+[[Category: Large Structures]]
 [[Category: Gazi, A]]
 [[Category: Pagare, P P]]