Cristina Fernández

University of Iowa, Iowa City, Iowa, United States

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Publications (2)4.38 Total impact

  • Liusheng Huang, Cristina Fernández, Robert J Kerns
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    ABSTRACT: Replacing N-sulfo groups in heparin with N-arylacyl moieties has been shown to afford charge-reduced heparin derivatives that maintain affinity for select heparin-binding proteins. In this study 50% and 100% N-desulfonated heparins were selectively N-acylated with phenylacetic acid and four phenylacetic acid analogs where the phenyl ring was replaced by a heterocycle. Protein-binding studies reveal that structural differences in the ring systems of the N-acyl groups appended to heparin afford significant affects on affinity and selectivity for different heparin-binding proteins.
    Bioorganic & Medicinal Chemistry Letters 02/2007; 17(2):419-23. · 2.34 Impact Factor
  • Cristina Fernández, Christopher M Hattan, Robert J Kerns
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    ABSTRACT: The glycosaminoglycan heparin is a polyanionic polysaccharide most recognized for its anticoagulant activity. Heparin binds to cationic regions in hundreds of prokaryotic and eukaryotic proteins, termed heparin-binding proteins. The endogenous ligand for many of these heparin-binding proteins is a structurally similar glycosaminoglycan, heparan sulfate (HS). Chemical and biosynthetic modifications of heparin and HS have been employed to discern specific sequences and charge-substitution patterns required for these polysaccharides to bind specific proteins, with the goal of understanding structural requirements for protein binding well enough to elucidate the function of the saccharide-protein interactions and/or to develop new or improved heparin-based pharmaceuticals. The most common modifications to heparin structure have been alteration of sulfate substitution patterns, carboxyl reduction, replacement N-sulfo groups with N-acetyl groups, and chain fragmentation. However, an accumulation of reports over the past 50 years describe semi-synthetic heparin derivatives obtained by incorporating aliphatic, aryl, and heteroaryl moieties into the heparin structure. A primary goal in many of these reports has been to identify heparin-derived structures as new or improved heparin-based therapeutics. Presented here is a perspective on the introduction of non-anionic structural motifs into heparin structure, with a focus on such modifications as a strategy to generate novel reduced-charge heparin-based bind-and-block antagonists of HS-protein interactions. The chemical methods employed to synthesize such derivatives, as well as other unique heparin conjugates, are reviewed.
    Carbohydrate Research 08/2006; 341(10):1253-65. · 2.04 Impact Factor