Synthetic receptors for membrane phospholipids have important applications in molecular imaging and targeting of biological processes. Detection of abnormal cell death in diseased cells and tissue using high-affinity small-molecule imaging agents remains a priority. Some success have been achieved by designing agents that target the aminophospholipid phosphatidylserine (PS) which along with phosphatidylethanolamine (PE) is exposed on the exterior surface of dying cells. Our group is seeking ways to improve binding affinity and selectivity of a probe while maintaining good in vivo properties. We have previously investigated systems based on bis-Zn(II)-dipicolylamine (Zn-DPA) coordination complexes and shown that the Zn-DPA probes can be improved by both covalent modification of a single Zn-DPA and by preparation of multivalent systems. The present study further explores the effect of multivalency on membrane recognition by using covalently-linked affinity groups acting as a) homoditopic receptors (two identical receptors) for PS and b) heteroditopic receptors (two different receptors) for PS alone or both PS and PE. We show that this multivalent approach grants some control over both binding kinetics and cell penetration and that these systems show promise for biomedical applications in the future.

Multivalent molecular recognition of membranes containing aminophospholipids

247th National Meeting (2014)

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