Design and Synthesis of E-Selectin Antagonists

Beat Ernst*, Zorica Dragic, Sébastien Marti, Christian Müller, Beatrice Wagner, Wolfgang Jahnke, John L. Magnani, Keith E. Norman, Reinhold Oehrlein, Thomas Peters, Hartmuth C. Kolb

*Corresponding author for this work
10 Citations (Scopus)


Selectin-mediated recruitment of leukocytes plays a crucial role in a number of diseases and pathological situations, for example in inflammation, reperfusion injury, rheumatoid arthritis and respiratory diseases. Substantial research efforts are directed toward development of carbohydrate-derived drugs that interfere with the inflammatory response by blocking the selectin binding site. This article describes two approaches for the improvement of the inhibitory potency of the lead structure sialyl Lewisx (sLex). One approach is based on the preorganization of mimics in their bioactive conformation to reduce entropic costs. For the conformational analysis of mimics, molecular modeling based tools were developed. They allow the rational design of selectin antagonists with simplified structures, but increased inhibitory potency. Alternatively, additional carbohydrate/lectin contacts can be identified for the improvement of enthalpic contributions. Following this approach, an additional hydrophobic interaction of the antagonists with E-selectin leads to a 60-fold improvement of E-selectin affinity. Antagonists have been synthesized using chemical or chemo-enzymatic methods. Finally, a flow chart for the biological evaluation of the antagonists is presented.

Original languageEnglish
Issue number4
Pages (from-to)268-274
Number of pages7
Publication statusPublished - 2001

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)


Dive into the research topics of 'Design and Synthesis of E-Selectin Antagonists'. Together they form a unique fingerprint.

Cite this