Department of Chemistry, Brandeis University, 415 South Street MS 015, Waltham, Massachusetts 02454, United States.
J Am Chem Soc. 2021 Jun 16;143(23):8565-8571. doi: 10.1021/jacs.1c03194. Epub 2021 Jun 7.
Carbohydrate binding proteins (CBPs) are attractive targets in medicine and biology. Multivalency, with several glycans binding to several binding pockets in the CBP, is important for high-affinity interactions. Herein, we describe a novel platform for design of multivalent carbohydrate cluster ligands by directed evolution, in which serum-stable 2'-fluoro modified RNA (F-RNA) backbones evolve to present the glycan in optimal clusters. We have validated this method by the selection of oligomannose (Man) glycan clusters from a sequence pool of ∼10 that bind to broadly neutralizing HIV antibody 2G12 with 13 to 36 nM affinities.
碳水化合物结合蛋白 (CBPs) 是医学和生物学中有吸引力的靶标。多价性，即几个糖与 CBP 中的几个结合口袋结合，对于高亲和力相互作用很重要。在此，我们通过定向进化描述了一种用于设计多价碳水化合物簇配体的新型平台，其中血清稳定的 2'-氟修饰 RNA (F-RNA) 骨架进化以呈现最佳簇中的糖。我们已经通过从结合广泛中和 HIV 抗体 2G12 的约 10 个序列池中选择寡甘露糖 (Man) 糖簇来验证该方法，其亲和力为 13 至 36 nM。
