Ribeiro João P, Villringer Sarah, Goyard David, Coche-Guerente Liliane, Höferlin Manuela, Renaudet Olivier, Römer Winfried, Imberty Anne
Univ. Grenoble Alpes , CNRS , CERMAV , 38000 Grenoble , France . Email:
Univ. Grenoble Alpes , CNRS , DCM , 38000 Grenoble , France.
Chem Sci. 2018 Aug 14;9(39):7634-7641. doi: 10.1039/c8sc02730g. eCollection 2018 Oct 21.
We engineered the first chimeric, bispecific lectin, with two rationally oriented and distinct recognition surfaces. This lectin, coined Janus lectin in allusion to the two-faced roman god, is able to bind independently to both fucosylated and sialylated glycoconjugates. The multivalent presentation of binding sites on each face of the Janus lectin is very efficient, resulting in avidities in the low nanomolar range for both fucosylated and sialylated surfaces. Moreover, novel heterovalent, bifunctional glycoclusters were synthetized that match the topology of the Janus lectin. Based on these tools, we constructed organized and controlled supramolecular architectures by assembling Janus lectin and glycocompound layer-by-layer. Furthermore, the Janus lectin was employed as biomolecular linker to organize protocells made from giant unilamellar vesicles of different nature, to more complex prototissues. In summary, tailor-made Janus lectins open wide possibilities for creating biomimetic matrices or artificial tissues.
我们设计了首个嵌合双特异性凝集素,其具有两个合理定向且不同的识别表面。这种凝集素因借鉴两面罗马神而被命名为“两面神凝集素”,能够独立结合岩藻糖基化和唾液酸化的糖缀合物。两面神凝集素每个表面上结合位点的多价呈现非常高效,对岩藻糖基化和唾液酸化表面的亲和力均处于低纳摩尔范围。此外,还合成了与两面神凝集素拓扑结构相匹配的新型异价双功能糖簇。基于这些工具,我们通过逐层组装两面神凝集素和糖化合物构建了有序且可控的超分子结构。此外,两面神凝集素被用作生物分子连接体,将由不同性质的巨型单层囊泡制成的原始细胞组织成更复杂的原始组织。总之,定制的两面神凝集素为创建仿生基质或人工组织开辟了广阔的可能性。