Multivalent display of quinic acid based ligands for targeting E-selectin expressing cells

Yosi Shamay, Denise Paulin, Gonen Ashkenasy, Ayelet David

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

The site-specific expression of molecular markers on endothelial cells of blood vessels during inflammatory response and angiogenesis provides an opportunity to target drugs and imaging molecules to the vascular endothelium of diseased tissues. This paper describes an innovative strategy for selective delivery of polymer conjugates to E- and P-selectin expressing cells using a series of quinic acid (Qa) based non-carbohydrate analogues of the natural ligand sialyl Lewisx (sLex) as targeting moieties. We demonstrate that such analogues antagonize the adhesion of sLex expressing HL-60 cells to both E- and P-selectin. Significantly, the apparent avidity of polymer conjugates carrying multiple Qa copies has increased by 3 orders of magnitude relative to their monomeric forms. Furthermore, we found that the major mechanism of copolymer entry and delivery into E-selectin expressing cells is endocytosis. These selectin-targetable copolymers provide the foundation to support controlled delivery of anticancer drugs and imaging agents to tumor vasculature for therapeutic and diagnostic applications.

Original languageEnglish
Pages (from-to)5906-5915
Number of pages10
JournalJournal of Medicinal Chemistry
Volume52
Issue number19
DOIs
StatePublished - 8 Oct 2009

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