Effects of side chain configuration and backbone spacing on the gene delivery properties of lysine-derived cationic oligomers and polymers

ORGN 388

Sarah E. Eldred, seeldred@wisc.edu1, Margaret R. Pancost2, Karin M. Otte3, David Rozema4, Shannon S. Stahl, stahl@chem.wisc.edu1, and Samuel H. Gellman1. (1) Department of Chemistry, University of Wisconsin, Madison, WI 53706, (2) Department of Chemistry, University of Wisconsin, Madison, 1101 University Ave., Madison, WI 53706, (3) Department of Chemistry, University of Wisconsin-Madison, 1101 University Ave., Madison, WI 53706, (4) Mirusbio Corporation, 505 S. Rosa Rd. suit 104, Madison, WI 53719
A series of lysine-based oligomers (18 residues) that differ in side chain configuration or side chain separation along the backbone was tested for DNA transfection activity. The oligomer constructed from b3-homolysine (b3hLys) and that from a-D-lysine were superior to an a-L-lysine 18-mer in gene delivery assays. This improved activity is attributed to the fact that the a-L-peptide is a protease substrate and can thus be degraded while the other 18-mers are not susceptible to proteolytic degradation. Poly(b3-hLys) was synthesized via ring opening polymerization of the corresponding lactam. The DNA transfection ability of this polymer was compared with that of commercially available poly(L-lysine) (PLL) and poly(D-lysine) (PDL). In each case the polymer was more active than the corresponding 18-mer.
 

Proteins, Peptides, Amino Acids, and Enzymes
8:00 AM-11:40 AM, Tuesday, 15 March 2005 Convention Center -- Room 9, Oral

Division of Organic Chemistry

The 229th ACS National Meeting, in San Diego, CA, March 13-17, 2005