A Self-Assembled Multivalent Pseudopolyrotaxane for Binding Galectin-1 Alshakim Nelson, † Jason M. Belitsky, † Se ´ bastien Vidal, § C. Steven Joiner, † Linda G. Baum,* ,‡ and J. Fraser Stoddart* ,† Contribution from the California NanoSystems Institute (CNSI), the Department of Chemistry and Biochemistry, and the Department of Pathology, UniVersity of California, Los Angeles, California 90095 Received February 17, 2004; E-mail: lbaum@mednet.ucla.edu; stoddart@chem.ucla.edu Abstract: A self-assembled pseudopolyrotaxane consisting of lactoside-displaying cyclodextrin (CD) “beads” threaded onto a linear polyviologen “string” was investigated for its ability to inhibit galectin-1-mediated T-cell agglutination. The CDs of the pseudopolyrotaxane are able to spin around the axis of the polymer chain as well as to move back and forth along its backbone to alter the presentation of its ligand. This supramolecular superstructure incorporates all the advantages of polymeric structures, such as the ability to span large distances, along with a distinctively dynamic presentation of its lactoside ligands to afford a neoglycoconjugate that can adjust to the relative stereochemistries of the lectin’s binding sites. The pseudopolyrotaxane exhibited a valency-corrected 10-fold enhancement over native lactose in the agglutination assay, which was greater than the enhancements observed for lactoside-bearing trivalent glycoclusters and a lactoside-bearing chitosan polymer tested using the same assay. The experimental results indicate that supramolecular architectures, such as the pseudopolyrotaxane, provide tools for investigating protein-carbohydrate interactions. Phenomena that control the form and function of living systems, such as self-assembly, 1 molecular recognition, 2 and multivalency, 3 have served to hasten the development of supramolecular chemistry 4 and template-directed synthesis, 5 particularly of mechanically interlocked molecular compounds. 6 Once considered chemical curiosities, complexes such as pseudorotaxanes 7 and compounds such as catenanes 8 and rotaxanes 9 are now contributing to advances in molecular electronics 10 and the construction of artificial molecular ma- chines. 11 In addition, polymeric pseudorotaxanes 12 and mechani- cally interlocked polyrotaxanes 13 are enriching polymer chem- istry and materials science in terms of both structure 14 and function. 15 While biology has provided much of the inspiration † California NanoSystems Institute and Department of Chemistry and Biochemistry, University of California, Los Angeles, CA. ‡ Department of Pathology, University of California, Los Angeles, CA. § Current address: Laboratoire de Chimie Organique 2, Universite Claude Bernard Lyon 1, France. 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