Lectin antagonists in infection, immunity, and inflammation.

Lectin antagonists in infection, immunity, and inflammation. Curr Opin Chem Biol. 2019 Aug 27;53:51-67 Authors: Meiers J, Siebs E, Zahorska E, Titz A Abstract Lectins are proteins found in all domains of life with a plethora of biological functions, especially in the infection process, immune response, and inflammation. Targeting these carbohydrate-binding proteins is challenged by the fact that usually low affinity interactions between lectin and glycoconjugate are observed. Nature often circumvents this process through multivalent display of ligand and lectin. Consequently, the vast majority of synthetic antagonists are multivalently displayed native carbohydrates. At the cost of disadvantageous pharmacokinetic properties and possibly a reduced selectivity for the target lectin, the molecules usually possess very high affinities to the respective lectin through ligand epitope avidity. Recent developments include the advent of glycomimetic or allosteric small molecule inhibitors for this important protein class and their use in chemical biology and drug research. This evolution has culminated in the transition of the small molecule GMI-1070 into clinical phase III. In this opinion article, an overview of the most important developments of lectin antagonists in the last two decades with a focus on the last five years is given. PMID: 31470348 [PubMed - as supplied by publisher]
Source: Current Opinion in Chemical Biology - Category: Biochemistry Authors: Tags: Curr Opin Chem Biol Source Type: research

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