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4A3-Cit

Version 1.0431a111 · 2026-09-13

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CAS No.Not available
Chemical Name4A3-Cit
Synonyms4A3Cit, 4A3 Cit
SMILESO=C(CCN(CCCN(CCCN(CCC(OCCOC(C(CSCCC(CC/C=C(C)/C)C)C)=O)=O)CCC(OCCOC(C(CSCCC(CC/C=C(C)/C)C)C)=O)=O)C)CCC(OCCOC(C(CSCCC(CC/C=C(C)/C)C)C)=O)=O)OCCOC(C(CSCCC(CC/C=C(C)\C)C)C)=O
FormulaC83H147N3O16S4
M.Wt1,571.33
Purity98%
StorageOriginal product: up to 1 year under the storage conditions stated on the vial, kept tightly sealed. Stock solutions: aliquots at -20°C, generally up to one month.
Shipping conditionShips from Shanghai. Pure lipid is stable during ice-pack transport.
PublicationS. M. Lee, Q. Cheng, X. L. Yu, S. Liu, L. T. Johnson, D. J. Siegwart, Angew. Chem. Int. Ed. 2021, 60, 5848.

4A3-Cit is an ionizable lipid used for the generation of lipid nanoparticles (LNPs). To investigate the role of unsaturated lipid tails in iLNPs, the nucleophilic amines were added to ester-based linkers, followed by Michael’s addition to the thiols to construct a library of 91 amino ionizable lipids. Such ionizable lipids were composed of an ionizable tertiary amine core, an ester-based degradable linker, and an alkylthiol tail periphery. Through in vitro and in vivo screening, the iLNPs with 4A3 core and citronellolbased (Cit) periphery can significantly increase endosome escape and delivery efficiency of mRNA, leading to 18-fold increase in protein expression compared with iLNPs without Cit periphery. Furthermore, the delivery efficiency of mRNA may be associated with the location/configuration of the unsaturated bond(s) in lipids. Although lipids with Cit periphery showed excellent membrane fusion ability to facilitate endosome escape, the fusion mechanism needs to be further clarified.

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