Surface Control of Thermosetting Fluorinated Polyurethane

In this paper, thermosetting fluorine-containing polyurethane (S-FPU) was synthesized through a novel method with two-step process and its surface properties was studied. Firstly, fluorine-containing epoxy compound (FO) was obtained by epichlorohydrin (ECH) and tetrafluoropropanol (TFP). Further, the fluorinated polyether polyols (FPO) was synthesized by cationic copolymerization of tetrahydrofuran (THF) with the FO, the fluorine was located on the side chains of the FPO and the molecular weight of FPO was controllable, besides, the molecular weight distribution of FPO was narrow. Finally, the S-FPU was prepared by FPO as soft segment, MDI as a hard segment and TEA as chain extender. The influence of fluorine enrichment on the surface properties of S-FPU was studied by controlling curing temperature, curing time and structure of FPO. In addition, the surface fluorine content of S-FPU and the surface hydrophobicity were studied in detail. The results showed that with the curing temperature decreased, the surface fluorine content of S-FPU increased, and when the curing time was more than 10 hours, the fluorine element did not migrate to the surface. What’s more, with the molecular weight of FPO increased, the surface fluorine content of S-FPU increased

Surface Control of Thermosetting Fluorinated Polyurethane

In this paper, thermosetting fluorine-containing polyurethane (S-FPU) was synthesized through a novel method with two-step process and its surface properties was studied. Firstly, fluorine-containing epoxy compound (FO) was obtained by epichlorohydrin (ECH) and tetrafluoropropanol (TFP). Further, the fluorinated polyether polyols (FPO) was synthesized by cationic copolymerization of tetrahydrofuran (THF) with the FO, the fluorine was located on the side chains of the FPO and the molecular weight of FPO was controllable, besides, the molecular weight distribution of FPO was narrow. Finally, the S-FPU was prepared by FPO as soft segment, MDI as a hard segment and TEA as chain extender. The influence of fluorine enrichment on the surface properties of S-FPU was studied by controlling curing temperature, curing time and structure of FPO. In addition, the surface fluorine content of S-FPU and the surface hydrophobicity were studied in detail. The results showed that with the curing temperature decreased, the surface fluorine content of S-FPU increased, and when the curing time was more than 10 hours, the fluorine element did not migrate to the surface. What’s more, with the molecular weight of FPO increased, the surface fluorine content of S-FPU increased

Structure and Function of Flavivirus NS5 Methyltransferase

The plus-strand RNA genome of flavivirus contains a 5′ terminal cap 1 structure (m(7)GpppAmG). The flaviviruses encode one methyltransferase, located at the N-terminal portion of the NS5 protein, to catalyze both guanine N-7 and ribose 2′-OH methylations during viral cap formation. Representative flavivirus methyltransferases from dengue, yellow fever, and West Nile virus (WNV) sequentially generate GpppA → m(7)GpppA → m(7)GpppAm. The 2′-O methylation can be uncoupled from the N-7 methylation, since m(7)GpppA-RNA can be readily methylated to m(7)GpppAm-RNA. Despite exhibiting two distinct methylation activities, the crystal structure of WNV methyltransferase at 2.8 Å resolution showed a single binding site for S-adenosyl-l-methionine (SAM), the methyl donor. Therefore, substrate GpppA-RNA should be repositioned to accept the N-7 and 2′-O methyl groups from SAM during the sequential reactions. Electrostatic analysis of the WNV methyltransferase structure showed that, adjacent to the SAM-binding pocket, is a highly positively charged surface that could serve as an RNA binding site during cap methylations. Biochemical and mutagenesis analyses show that the N-7 and 2′-O cap methylations require distinct buffer conditions and different side chains within the K(61)-D(146)-K(182)-E(218) motif, suggesting that the two reactions use different mechanisms. In the context of complete virus, defects in both methylations are lethal to WNV; however, viruses defective solely in 2′-O methylation are attenuated and can protect mice from later wild-type WNV challenge. The results demonstrate that the N-7 methylation activity is essential for the WNV life cycle and, thus, methyltransferase represents a novel target for flavivirus therapy

West Nile Virus Methyltransferase Catalyzes Two Methylations of the Viral RNA Cap through a Substrate-Repositioning Mechanism▿

Flaviviruses encode a single methyltransferase domain that sequentially catalyzes two methylations of the viral RNA cap, GpppA-RNA→m7GpppA-RNA→m7GpppAm-RNA, by using S-adenosyl-l-methionine (SAM) as a methyl donor. Crystal structures of flavivirus methyltransferases exhibit distinct binding sites for SAM, GTP, and RNA molecules. Biochemical analysis of West Nile virus methyltransferase shows that the single SAM-binding site donates methyl groups to both N7 and 2′-O positions of the viral RNA cap, the GTP-binding pocket functions only during the 2′-O methylation, and two distinct sets of amino acids in the RNA-binding site are required for the N7 and 2′-O methylations. These results demonstrate that flavivirus methyltransferase catalyzes two cap methylations through a substrate-repositioning mechanism. In this mechanism, guanine N7 of substrate GpppA-RNA is first positioned to SAM to generate m7GpppA-RNA, after which the m7G moiety is repositioned to the GTP-binding pocket to register the 2′-OH of the adenosine with SAM, generating m7GpppAm-RNA. Because N7 cap methylation is essential for viral replication, inhibitors designed to block the pocket identified for the N7 cap methylation could be developed for flavivirus therapy