title: Disubstituted Sialic Acid Ligands Targeting Siglecs CD33 and CD22 Associated with Myeloid Leukaemias and B Cell Lymphomas.
abstract: The siglec family of sialic acid-binding proteins are endocytic immune cell receptors that are recognized as potential targets for cell directed therapies. CD33 and CD22 are prototypical members and are validated candidates for targeting acute myeloid leukaemia and non-Hodgkin's lymphomas due to their restricted expression on myeloid cells and B-cells, respectively. While nanoparticles decorated with high affinity siglec ligands represent an attractive platform for delivery of therapeutic agents to these cells, a lack of ligands with suitable affinity and/or selectivity has hampered progress. Herein we describe selective ligands for both of these siglecs, which when displayed on liposomal nanoparticles, can efficiently target the cells expressing them in peripheral human blood. Key to their identification was the development of a facile method for chemo-enzymatic synthesis of disubstituted sialic acid analogues, combined with iterative rounds of synthesis and rapid functional analysis using glycan microarrays.
authors.affiliation: Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037 (USA) ; Department of Chemical Physiology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037 (USA).
authors.forename: Cory D
authors.initials: CD
authors.lastname: Rillahan
authors.affiliation: Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037 (USA) ; Department of Chemical Physiology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037 (USA).
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Macauley
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037 (USA).
authors.forename: Erik
authors.initials: E
authors.lastname: Schwartz
authors.affiliation: Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037 (USA) ; Department of Chemical Physiology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037 (USA).
authors.forename: Yuan
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037 (USA) ; Department of Chemical Physiology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037 (USA).
authors.forename: Ryan
authors.initials: R
authors.lastname: McBride
authors.affiliation: Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037 (USA) ; Department of Chemical Physiology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037 (USA).
authors.forename: Britni M
authors.initials: BM
authors.lastname: Arlian
authors.affiliation: Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037 (USA) ; Department of Chemical Physiology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037 (USA).
authors.forename: Janani
authors.initials: J
authors.lastname: Rangarajan
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037 (USA).
authors.forename: Valery V
authors.initials: VV
authors.lastname: Fokin
authors.affiliation: Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037 (USA) ; Department of Chemical Physiology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037 (USA).
authors.forename: James C
authors.initials: JC
authors.lastname: Paulson