Low molecular weight disulfide cross-linking peptides as nonviral gene delivery carriers.
Cross-linking peptides have been developed by inserting multiple Cys residues into a 20 amino acid condensing peptide that polymerizes through disulfide bond formation when bound to DNA resulting in small, highly stable DNA condensates that mediate efficient in vitro gene transfer [McKenzie et al. (2000) J. Biol. Chem. 275, 9970-9977]. In the present study, a minimal peptide of four Lys and two terminal Cys residues was found to substitute for Cys-Trp-(Lys)(17)-Cys, resulting in DNA condensates with similar particle size and gene expression in HepG2 cells. Substitution of His for Lys residues resulted in an optimal peptide of Cys-His-(Lys)(6)-His-Cys that, in addition to the attributes described above, also provided buffering capacity to enhance in vitro gene expression in the absence of chloroquine. The reported structure-activity relationships systematically explore peptides with combinations of Lys, Cys, and His residues resulting in low molecular weight peptides with improved gene transfer properties.
McKenzie
D L
DL
Divisions of Medicinal Chemistry and Pharmaceutics, College of Pharmacy University of Michigan, Ann Arbor, Michigan 48109-165, USA.
Smiley
E
E
Kwok
K Y
KY
Rice
K G
KG
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004220:Disulfides / Q000737:chemistry*; D018014:Gene Transfer Techniques; D006801:Humans; D007700:Kinetics; D008970:Molecular Weight; D010455:Peptides / Q000737:chemistry*
D003432:Cross-Linking Reagents; D004220:Disulfides; D010455:Peptides