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Disubstituted sialic acid ligands targeting siglecs CD33 and CD22 associated with myeloid leukaemias and B cell lymphomas

Academic Article
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Overview

related to degree

  • Rillahan, Cory, Ph.D. in Biology, Scripps Research 2007 - 2012

authors

  • Rillahan, Cory
  • Macauley, Matthew
  • Schwartz, E.
  • He, Y.
  • McBride, R.
  • Arlian, B. M.
  • Rangarajan, J.
  • Fokin, Valery
  • Paulson, James

publication date

  • 2014

journal

  • Chemical Science  Journal

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.
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Identity

PubMed Central ID

  • PMC4048721

International Standard Serial Number (ISSN)

  • 2041-6520

Digital Object Identifier (DOI)

  • 10.1039/c4sc00451e

PubMed ID

  • 24921038
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Additional Document Info

start page

  • 2398

end page

  • 2406

volume

  • 5

issue

  • 6

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