Disubstituted Sialic Acid Ligands Targeting Siglecs CD33 and CD22 Associated with Myeloid Leukaemias and B Cell Lymphomas

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 t...

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Bibliographic Details
Published in:Chemical science (Cambridge) 2014-01, Vol.5 (6), p.2398-2406
Main Authors: Rillahan, Cory D, Macauley, Matthew S, Schwartz, Erik, He, Yuan, McBride, Ryan, Arlian, Britni M, Rangarajan, Janani, Fokin, Valery V, Paulson, James C
Format: Article
Language:English
Subjects:
Affinity
Glycan
Leukaemia
Ligands
Nanoparticles
Synthesis
Target recognition
Therapy
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Summary: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.
ISSN:2041-6520
2041-6539
DOI:10.1039/c4sc00451e