STRATEGIES FOR DELIVERY: I: Synthesis and Applications of Endcapped Oligonucleotides II: Synthesis and Delivery of Amine and Guanidinium Functionalized Gold Nanoparticles

Part I: Endcaps are linkers that link the 3? and 5? ends of DNA duplexes. A series of diamide endcaps has been synthesized and shown to stabilize DNA duplexes (4 base-pair). Endcapped CpG oligonucleotides were synthesized to elucidate the mode of recognition of different forms of CpG oligonucleotides by the immune system. Endcapped CpG oligonucleotides stimulated IL-6 and IL-12 secretion and extended the life span of the tumor implanted mice beyond that of the untreated control mice. Closed endcapped DNA duplexes were obtained by enzymatic ligation of the nicked DNA duplexes. The efficiency of ligation was dependent on the number of nucleotides flanking the 3?- and 5? ends of the nick. The nuclease stability of endcapped CpG oligonucleotides was established to be at least 6- fold more stable than unmodified oligonucleotides. Part II: Thiol terminated amine and guanidinium derivatives were synthesized and conjugated to 5 nm and 10 nm gold nanoparticles. These functionalized gold colloids were studied for their cellular uptake.

Pei-Sze Ng joined a biotechnology company in Cambridge, MA, as a scientist after completion of her post-doctorate training at the Massachusetts Institute of Technology. From 1999 to 2004, she did her doctoral work in the field of medicinal chemistry and biotechnology at Purdue University, Indiana, U.S.A. Her family lives in Singapore.