Design, synthesis and evaluation of a tripodal receptor for phosphatidylinositol phosphates

Abstract

Phosphatidylinositol phosphates (PIPs) are membrane phospholipids that play crucial roles in a wide range of cellular processes. Their function is dictated by the number and positions of the phosphate groups in the inositol ring (with seven different PIPs being active in the cell). Therefore, there is significant interest in developing small-molecule receptors that can bind selectively to these species and in doing so affect their cellular function or be the basis for molecular probes. However, to date there are very few examples of such molecular receptors. Towards this aim, herein we report a novel tripodal molecule that acts as receptor for mono- and bis-phosphorylated PIPs in a cell free environment. To assess their affinity to PIPs we have developed a new cell free assay based on the ability of the receptor to prevent alkaline phosphatase from hydrolysing these substrates. The new receptor displays selectivity towards two out of the seven PIPs, namely PI(3)P and PI(3,4)P2. To rationalise these results, a DFT computational study was performed which corroborated the experimental results and provided insight into the host–guest binding mode.

Myo-inositol supplementation in women of reproductive age with subclinical hypothyroidism and obesity on the background of vitamin D deficiency

“…Інозитол (вітамін В 8 ) -це циклічний шестиатомний спирт циклогексану (С 6 Н 12 О 6 ), який має 9 стереоізомерів [11,12]. Міо-інозитол та D-хіро-інозитол -це два основні стереоізомери інозиту, що утворюються після епімеризації гідроксильних груп інозитолу та мають інсуліносенситайзерні властивості [13]. Декілька досліджень продемонстрували, що міо-інозитол є попередником синтезу фосфоінозитидів, які є частиною шляху трансдукції сигналу фосфатидилінозитолу через плазматичну мембрану, за допомогою другого месенджера 1,4,5-трифосфату, який модулює внутрішньоклітинний викид Ca 2+ [14].…”

Expedient synthesis and luminescence sensing of the inositol pyrophosphate cellular messenger 5-PP-InsP5

“…Molecular receptors that elicit a luminescence response upon binding a specic guest can provide a rapid and sensitive method for quantifying target species in aqueous biological media and living cells. [11][12][13][14] Several molecular receptors for inositol phosphates in general have been developed for in vitro analyses; [15][16][17][18][19][20] however, to the best of our knowledge there are no examples of receptors selective for inositol pyrophosphates. Anslyn developed a receptor for inositol trisphosphates (InsP 3 s) based on organic scaffolds substituted with phosphaterecognition moieties such as guanidinium or imidazolium groups.…”

Biomass-Derived Core–Shell Carbon Dots with Embedded Tripodal Receptors for the Selective Recognition of Mefenamic Acid in Pharmaceutical Formulations and Urine

“…Tripodal receptors have been used in a wide range of applications based on host–guest chemistry. − These receptors are exceptionally magnificent as they are known for encapsulating particular species by organizing their spheroidal dimensions complementary to the size and shape of the analyte. − The flexibility and multifunctionality of the arms provide interactive sites to capture the analyte selectively from other structural analogues. Herein, a novel tripodal amine (TPA) having three arms equipped with –OH, N, and S donors is synthesized and incorporated onto the surface of fluorescent carbon dots (FCDs) within a mesoporous silica network for the selective recognition of mefenamic acid (MFA).…”