Spatial Screening of Lectin Ligands : Cyclic Peptides as Scaffolds for Multivalent Presentation of Carbohydrates

Abstract

Carbohydrate-lectin interactions are the basis of numerous biologically important recognition processes. Examples include the initiation of the inflammatory response, bacterial and viral pathogenesis, fertilization, and even protein folding. High-affinity lectin ligands are of considerable medicinal interest in the diagnosis, therapy, and prevention of conditions associated with these processes. One approach to arrive at such ligands is the design of small oligovalent carbohydrate derivatives (mini clusters) which can simultaneously bind to several binding sites of a single (oligomeric) lectin proximate in space and may be tailored to lectins with known 3D-structure ( directed multivalency). However, if the structure of the targeted lectin and thus the required orientation of the sugar epitopes of the mini clusters are unknown, an efficient procedure for the generation and screening of libraries of spatially diverse mini clusters is desirable. Here we present a new strategy for finding multivalent lectin ligands by spatial screening using libraries of cyclic peptides as scaffolds for multivalent presentation of carbohydrate epitopes.