Bio-orthogonal phosphatidylserine conjugates for delivery and imaging applications.
The syntheses of phosphatidylserine (PS) conjugates are described, including fluorescent derivatives for potential cellular delivery and bioimaging applications. Installation of terminal functional groups (amine, thiol, or alkyne) onto the sn-2 chain provides reactive sites for bio-orthogonal conjugation of cargo with suitably protected PS derivatives. An amine-containing PS forms amide bonds with peptidic cargo, a thiol derivative is designed for conjugation to cargo that contain alpha-halo carbonyls or Michael acceptors, and the terminal alkyne PS analogue permits "click" conjugation with any azide-tagged molecule. This latter conjugation method is quite versatile as it can be performed without PS headgroup protection, in aqueous media, and with acid-labile cargo.
Lampkins
Andrew J
AJ
Department of Chemistry and Biochemistry and Walther Cancer Research Center, 251 Nieuwland Science Hall, University of Notre Dame, Notre Dame, Indiana 46556, USA.
O'Neil
Edward J
EJ
Smith
Bradley D
BD
D000480:Alkynes / Q000138:chemical synthesis / Q000737:chemistry; D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry; D001386:Azides / Q000138:chemical synthesis / Q000737:chemistry; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry; D010713:Phosphatidylcholines / Q000737:chemistry; D010718:Phosphatidylserines / Q000138:chemical synthesis* / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry
D000480:Alkynes; D000588:Amines; D001386:Azides; D005456:Fluorescent Dyes; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; D013438:Sulfhydryl Compounds