Intracellular Delivery and Triggered Release of DNA Using Biodegradable Poly(2-hydroxypropylene imine)s Containing Cystamine Units.

Poly(2-hydroxypropylene imine)s containing segments of cystamine (PHPI-CA) are synthesized by polycondensation of 1,3-dibromo-2-propanol with a mixture of 1,3-diamino-2-propanol and cystamine. High molecular weight fractions of these polymers are collected by ultrafiltration and characterized by chemical analysis, H and C-NMR spectroscopy, size-exclusion chromatography with triple detection, and potentiometric titration, and are tested for DNA delivery in vitro. It is shown that PHPI-CA are highly branched polymers containing disulfide linkages.

Efficient gene transfection using novel cationic polymers poly(hydroxyalkylene imines).

A series of novel cationic polymers poly(hydroxyalkylene imines) were synthesized and tested for their ability to transfect cells in vitro and in vivo. Poly(hydroxyalkylene imines), in particular, poly(2-hydroxypropylene imine) (pHP), poly(2-hydroxypropylene imine ethylene imine) (pHPE), and poly(hydroxypropylene imine propylene imine) (pHPP) were synthesized by polycondensation reaction from 1,3-diamino-2-propanol and the appropriate dibromide. Electron microscopic examination demonstrated that the resulting polymers condensed DNA into toroid shape complexes of 100-150 nm in size.

The fluoride cleavable 2-(cyanoethoxy)methyl (CEM) group as reversible 3'-O-terminator for DNA sequencing-by-synthesis - synthesis, incorporation, and cleavage.

A new and promising sequencing technology called sequencing-by-synthesis (SBS) enables fast determination of DNA sequences. 2'-Deoxynucleotides containing the (2-cyanoethoxy)methyl (CEM) group at the 3'-O-position are potential reversible terminators for the SBS technology. Herein we describe the synthesis, the incorporation by several polymerases, and the cleavage of this 3'-O-blocking group using 3'-O-CEM-thymidinyl-5'-O-triphosphate 7 as an example.

Radical amination with sulfonyl azides: a powerful method for the formation of C-N bonds.

A novel reaction for the introduction of an azide moiety by means of a mild radical process is currently under development. Sulfonyl azides are suitable azidating agents for nucleophilic radicals, such as secondary and tertiary alkyl radicals. More electrophilic radicals, such as enolate radicals, do not react with sulfonyl azides.

Radical carboazidation: expedient assembly of the core structure of various alkaloid families.

A procedure for one-pot intermolecular radical addition of 2-iodoesters to terminal alkenes followed by azidation of the radical adduct has been developed. This sequential reaction represents an alkene carboazidation process. Its efficacy is demonstrated by the two-step preparation of various lactams such as pyrrolidinones, pyrrolizidinones, and indolizidinones.