Novel N7- and N1-substituted cGMP derivatives are potent activators of cyclic nucleotide-gated channels.

ABSTRACT: Cyclic nucleotide-gated (CNG) channels, key players in olfactory and visual signal transduction, generate electrical responses to odorant- and light-induced changes in cyclic nucleotide concentration. Previous work suggests that substitutions are tolerated solely at the C8 position on the purine ring of cGMP. Our studies with C8, 2'-OH, and 2-NH2-modified cGMP derivatives support this assertion. To gain further insight into determinants important for CNG channel binding and activation, we targeted previously unexplored positions. Modifications at N7 of 8-SH-cGMP (6) are well tolerated by olfactory and retinal rod CNG channels. Toleration of a very large substituent, a 3400 molecular weight PEG, at either N7 or C8 argues for broad accommodation at these positions in the binding site. Modifi

SUBMITTER: Strassmaier T 

PROVIDER: S-EPMC2597524 | biostudies-literature | 2007 Aug

REPOSITORIES: biostudies-literature