The author of 《The valency of fatty acid conjugates impacts siRNA pharmacokinetics, distribution, and efficacy in vivo》 were Biscans, Annabelle; Coles, Andrew; Echeverria, Dimas; Khvorova, Anastasia. And the article was published in Journal of Controlled Release in 2019. COA of Formula: C12H22F6N6OP2 The author mentioned the following in the article:
Lipid-conjugated small-interfering RNAs (siRNAs) exhibit accumulation and gene silencing in extrahepatic tissues, providing an opportunity to expand therapeutic siRNA utility beyond the liver. Chem. engineering lipids may further improve siRNA delivery and efficacy, but the relationship between lipid structure/configuration and siRNA pharmacodynamics is unclear. Here, we synthesized a panel of mono-, di-, and tri-meric fatty acid-conjugated siRNAs to systematically evaluate the impact of fatty acid structure and valency on siRNA clearance, distribution, and efficacy. Fatty acid valency significantly altered the physicochem. properties of conjugated siRNAs, including hydrophobicity and micelle formation, which affected distribution. Trivalent lipid-conjugated siRNAs were predominantly retained at the site of injection with minimal systemic exposure, whereas monovalent lipid-conjugated siRNAs were quickly released into the circulation and accumulated primarily in kidney. Divalent lipid-conjugated siRNAs showed intermediate behavior, and preferentially accumulated in liver with functional distribution to lung, heart, and fat. The chem. structure of the conjugate, rather than overall physicochem. properties (i.e. hydrophobicity), predicted the degree of extrahepatic tissue accumulation necessary for productive gene silencing. Our findings will inform chem. engineering strategies for enhancing the extrahepatic delivery of lipophilic siRNAs. In the experiment, the researchers used many compounds, for example, ((1H-Benzo[d][1,2,3]triazol-1-yl)oxy)tris(dimethylamino)phosphonium hexafluorophosphate(V)(cas: 56602-33-6COA of Formula: C12H22F6N6OP2)
((1H-Benzo[d][1,2,3]triazol-1-yl)oxy)tris(dimethylamino)phosphonium hexafluorophosphate(V)(cas: 56602-33-6) is a peptide coupling reagent. Can be used in the preparation of phenyl esters of amino acids which have been shown to be valuable as blocked derivatives of amino acids in the field of peptide synthesis.COA of Formula: C12H22F6N6OP2
Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics