Jump to main content
Jump to site search
PLANNED MAINTENANCE Close the message box

Scheduled maintenance upgrade on Thursday 4th of May 2017 from 8.00am to 9.00am (BST).

During this time our websites will be offline temporarily. If you have any questions please use the feedback button on this page. We apologise for any inconvenience this might cause and thank you for your patience.


Issue 27, 2014
Previous Article Next Article

Design and synthesis of lipid-coupled inositol 1,2,3,4,5,6-hexakisphosphate derivatives exhibiting high-affinity binding for the HIV-1 MA domain

Author affiliations

Abstract

The precursor of Gag protein (Pr55Gag) of human immunodeficiency virus, the principal structural component required for virus assembly, is known to bind D-myo-phosphatidylinositol 4,5-bisphosphate (PIP2). The N-terminus of Pr55Gag, the MA domain, plays a critical role in the binding of Pr55Gag to the plasma membrane. Herein, we designed and synthesized myo-phosphatidylinositol 2,3,4,5,6-pentakisphosphate (PIP5) derivatives comprising highly phosphorylated inositol and variously modified diacylglycerol to examine the MA-binding properties. The inositol moiety was synthesized starting with myo-inositol and assembled with a hydrophobic glycerol moiety through a phosphate linkage. The Kd value for MA-binding of the PIP5 derivative 2 (Kd = 0.25 μM) was the lowest (i.e., highest affinity) of all derivatives, i.e., 70-fold lower than the Kd for the PIP2 derivative 1 (Kd = 16.9 μM) and 100-fold lower than the Kd for IP6 (Kd = 25.7 μM), suggesting the possibility that the PIP5 derivative blocks Pr55Gag membrane binding by competing with PIP2 in MA-binding.

Graphical abstract: Design and synthesis of lipid-coupled inositol 1,2,3,4,5,6-hexakisphosphate derivatives exhibiting high-affinity binding for the HIV-1 MA domain

Back to tab navigation
Please wait while Download options loads

Supplementary files

Publication details

The article was received on 15 Feb 2014, accepted on 13 May 2014 and first published on 14 May 2014


Article type: Paper
DOI: 10.1039/C4OB00350K
Citation: Org. Biomol. Chem., 2014,12, 5006-5022
  •   Request permissions

    Design and synthesis of lipid-coupled inositol 1,2,3,4,5,6-hexakisphosphate derivatives exhibiting high-affinity binding for the HIV-1 MA domain

    H. Tateishi, K. Anraku, R. Koga, Y. Okamoto, M. Fujita and M. Otsuka, Org. Biomol. Chem., 2014, 12, 5006
    DOI: 10.1039/C4OB00350K

Search articles by author