Heparin Binding Proteins as Therapeutic Target: An Historical Account and Current Trends

Medicines
Giancarlo Ghiselli

Abstract

The polyanionic nature and the ability to interact with proteins with different affinities are properties of sulfated glycosaminoglycans (GAGs) that determine their biological function. In designing drugs affecting the interaction of proteins with GAGs the challenge has been to generate agents with high binding specificity. The example to emulated has been a heparin-derived pentasaccharide that binds to antithrombin-III with high affinity. However, the portability of this model to other biological situations is questioned on several accounts. Because of their structural flexibility, oligosaccharides with different sulfation and uronic acid conformation can display the same binding proficiency to different proteins and produce comparable biological effects. This circumstance represents a formidable obstacle to the design of drugs based on the heparin scaffold. The conceptual framework discussed in this article is that through a direct intervention on the heparin-binding functionality of proteins is possible to achieve a high degree of action specificity. This objective is currently pursued through two strategies. The first makes use of small molecules for which in the text we provide examples from past and present literature con...Continue Reading

References

Jan 20, 1994·Biochemical Pharmacology·M CiomeiN Mongelli
Sep 1, 1996·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·M SalmivirtaU Lindahl
Jun 29, 2000·Annual Review of Biochemistry·M BernfieldM Zako
Dec 5, 2000·Current Pharmaceutical Design·M BottaF Corelli
Dec 26, 2000·The Journal of Biological Chemistry·A E ProudfootT N Wells
Jan 12, 2002·Current Opinion in Structural Biology·L Pellegrini
Feb 12, 2002·Advances in Carbohydrate Chemistry and Biochemistry·B Casu, U Lindahl
Sep 21, 2002·Molecular and Cellular Biology·Brian K YehMoosa Mohammadi
Feb 7, 2003·Proceedings of the National Academy of Sciences of the United States of America·Amanda E I ProudfootMarie H Kosco-Vilbois
Jan 14, 2004·The Journal of Biological Chemistry·Asa Hagner-McWhirterUlf Lindahl
May 15, 2004·Molecular & Cellular Proteomics : MCP·LaToya S JonesC Russell Middaugh
May 20, 2004·Bioorganic & Medicinal Chemistry Letters·Stephen M CourtneyPaul R Turner
Jun 17, 2004·Angewandte Chemie·Maurice Petitou, Constant A A van Boeckel
Oct 21, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zoë JohnsonAmanda E I Proudfoot
Dec 3, 2004·Drug Discovery Today·Virginia L RathStefan Hemmerich
Apr 20, 2005·Bioorganic & Medicinal Chemistry Letters·Stephen M CourtneyPaul R Turner
Jun 15, 2005·Annual Review of Biochemistry·T M HandelA E Proudfoot
Sep 13, 2005·Current Opinion in Structural Biology·Moosa MohammadiRegina Goetz
Sep 22, 2005·Chembiochem : a European Journal of Chemical Biology·Siska CochranIan Bytheway
Jul 13, 2006·Annual Review of Biomedical Engineering·Ram SasisekharanVikas Prabhakar
Aug 1, 2006·Nature Chemical Biology·Cristal I GamaLinda C Hsieh-Wilson
Aug 2, 2006·The Journal of Cell Biology·Johan KreugerUlf Lindahl
Sep 12, 2006·Journal of Thrombosis and Haemostasis : JTH·J R ToomeyJ A Erhardt
Jul 2, 2009·Molecular & Cellular Proteomics : MCP·Alessandro OriDavid G Fernig

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Citations

Jul 14, 2020·Reviews in Medical Virology·Paulo Ricardo CriadoJuarez Antonio Simões Quaresma
Apr 4, 2021·Biomolecules·Aikaterini BerdiakiDragana Nikitovic
May 20, 2021·Biochemistry (Moscow) Supplement. Series B, Biomedical Chemistry·L S LitvinovaI A Khlusov

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Methods Mentioned

BETA
xenografts
X-ray
surface plasmon resonance
glycosylation
sulfotransferases
sulfotransferase
NMR
bronchoalveolar lavage

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