title: Facile supermolecular aptamer inhibitors of L-selectin.
abstract: Multivalent interactions occur frequently in nature, where they mediate high-affinity interactions between cells, proteins, or molecules. Here, we report on a method to generate multivalent aptamers (Multi-Aptamers) that target L-selectin function using rolling circle amplification (RCA). We find that the L-selectin Multi-Aptamers have increased affinity compared to the monovalent aptamer, are specific to L-selectin, and are capable of inhibiting interactions with endogenous ligands. In addition, the Multi-Aptamers efficiently inhibit L-selectin mediated dynamic adhesion in vitro and homing to secondary lymphoid tissues in vivo. Importantly, our method of generating multivalent materials using RCA avoids many of the challenges associated with current multivalent materials in that the Multi-Aptamers are high affinity, easily produced and modified, and biocompatible. We anticipate that the Multi-Aptamers can serve as a platform technology to modulate diverse cellular processes.
authors.affiliation: Sue and Bill Gross Stem Cell Research Center, Chao Family Comprehensive Cancer Center, Edwards Lifesciences Center for Advanced Cardiovascular Technology, Edwards Lifesciences Center for Advanced Cardiovascular Technology, Department of Biomedical Engineering, and Department of Pharmaceutical Sciences, University of California Irvine, Irvine, California, 92697, United States of America.
authors.forename: Elizabeth K
authors.initials: EK
authors.lastname: Chang
authors.affiliation: Sue and Bill Gross Stem Cell Research Center, Chao Family Comprehensive Cancer Center, Edwards Lifesciences Center for Advanced Cardiovascular Technology, Edwards Lifesciences Center for Advanced Cardiovascular Technology, Department of Biomedical Engineering, and Department of Pharmaceutical Sciences, University of California Irvine, Irvine, California, 92697, United States of America.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Eckert
authors.affiliation: Sue and Bill Gross Stem Cell Research Center, Chao Family Comprehensive Cancer Center, Edwards Lifesciences Center for Advanced Cardiovascular Technology, Edwards Lifesciences Center for Advanced Cardiovascular Technology, Department of Biomedical Engineering, and Department of Pharmaceutical Sciences, University of California Irvine, Irvine, California, 92697, United States of America.
authors.forename: M Monsur
authors.initials: MM
authors.lastname: Ali
authors.affiliation: Sue and Bill Gross Stem Cell Research Center, Chao Family Comprehensive Cancer Center, Edwards Lifesciences Center for Advanced Cardiovascular Technology, Edwards Lifesciences Center for Advanced Cardiovascular Technology, Department of Biomedical Engineering, and Department of Pharmaceutical Sciences, University of California Irvine, Irvine, California, 92697, United States of America.
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Riazifar
authors.affiliation: Sue and Bill Gross Stem Cell Research Center, Chao Family Comprehensive Cancer Center, Edwards Lifesciences Center for Advanced Cardiovascular Technology, Edwards Lifesciences Center for Advanced Cardiovascular Technology, Department of Biomedical Engineering, and Department of Pharmaceutical Sciences, University of California Irvine, Irvine, California, 92697, United States of America.
authors.forename: Egest J
authors.initials: EJ
authors.lastname: Pone
authors.affiliation: Sue and Bill Gross Stem Cell Research Center, Chao Family Comprehensive Cancer Center, Edwards Lifesciences Center for Advanced Cardiovascular Technology, Edwards Lifesciences Center for Advanced Cardiovascular Technology, Department of Biomedical Engineering, and Department of Pharmaceutical Sciences, University of California Irvine, Irvine, California, 92697, United States of America.
authors.forename: Linan
authors.initials: L
authors.lastname: Liu
authors.affiliation: Sue and Bill Gross Stem Cell Research Center, Chao Family Comprehensive Cancer Center, Edwards Lifesciences Center for Advanced Cardiovascular Technology, Edwards Lifesciences Center for Advanced Cardiovascular Technology, Department of Biomedical Engineering, and Department of Pharmaceutical Sciences, University of California Irvine, Irvine, California, 92697, United States of America.
authors.forename: Weian
authors.initials: W
authors.lastname: Zhao
mesh_terms: D052157:Aptamers, Nucleotide / Q000494:pharmacology*; D006801:Humans; D019169:Jurkat Cells; D019041:L-Selectin / Q000187:drug effects* / Q000378:metabolism; D011485:Protein Binding
chemical_list: D052157:Aptamers, Nucleotide; D019041:L-Selectin
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