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Synthesis of Modular Headgroup Conjugates Corresponding to All Seven Phosphatidylinositol Polyphosphate Isomers for Convenient Probe Generation
Author(s) -
Gong Denghuang,
Bostic Heidi E.,
Smith Matthew D.,
Best Michael D.
Publication year - 2009
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200900476
Subject(s) - chemistry , phosphatidylinositol , conjugate , polyphosphate , stereochemistry , amine gas treating , chemical synthesis , combinatorial chemistry , signal transduction , biochemistry , organic chemistry , in vitro , mathematical analysis , mathematics , phosphate
Phosphatidylinositol polyphosphate lipids (PIP n s) play key roles in important biological pathways, and defects in the signaling activities of these molecules have been implicated in a number of disease states. As such, it is necessary to understand the complex roles of these lipids in biological pathways, which often involve their actions as site‐specific ligands that recruit receptors to the surfaces of cellular membranes. However, the complex structures of PIP n family members, of which seven biologically active isomers exist, complicate studies. Derivatized analogs of the PIP n structures are beneficial as chemical tools for elucidating signaling and binding activities. Herein, we present an efficient approach to probe the generation in which amino conjugates of PIP n headgroups can be conveniently functionalized in the final step of the synthesis to obtain a number of derivatized analogs of use for different studies. In addition to the application of this strategy to generate PI‐(4,5)‐P 2 headgroup probes, we also report the synthesis of PIP n –amine conjugates corresponding to all seven naturally existing isomers. This approach will be invaluable for generating the range of probe structures that is required to elucidate the intricacies of PIP n signaling. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)