title: Structure/function analysis of peptoid/lipitoid:DNA complexes.
abstract: Previous transfection studies of cationic peptoid polymers (N-substituted polyglycines) and cationic lipitoid polymers (peptoid-phospholipid conjugates) have shown that only the polymers which possessed a repeating (cationic, hydrophobic, hydrophobic) substituent sequence are efficient in gene transfer in vitro. To determine if there is a physical attribute of peptoid and lipitoid complexes that correlates with efficient gene transfection, biophysical, and transfection measurements were performed with polymer:DNA complexes containing each of seven structurally diverse peptoid polymers and two lipitoids that possess different hydrophobic substituents. These measurements revealed that the biophysical properties of these complexes (size, zeta-potential, ethidium bromide exclusion) varied with polymer structure and complex (+/-) charge ratio but were not directly predictive of transfection efficiency. Unique alterations in the circular dichroism spectra of DNA were observed in complexes containing several of the peptoids and both lipitoids, although FTIR spectroscopy demonstrated that the DNA remained in the B-form. The lack of correlations between the physical properties and the transfection activities of these polyplexes suggests that a further subpopulation examination of these complexes by these methods may reveal hidden structure-activity relationships.
authors.affiliation: Department of Pharmaceutical Chemistry, 2095 Constant Avenue, University of Kansas, Lawrence, Kansas 66047, USA.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Lobo
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Vetro
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Suich
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Zuckermann
authors.forename: C Russell
authors.initials: CR
authors.lastname: Middaugh
mesh_terms: D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002942:Circular Dichroism; D006224:Cricetinae; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers; D004996:Ethidium / Q000737:chemistry; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins; D006801:Humans; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D009690:Nucleic Acid Conformation; D010316:Particle Size; D034444:Peptoids / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D014162:Transfection
chemical_list: D004337:Drug Carriers; D008164:Luminescent Proteins; D034444:Peptoids; D010743:Phospholipids; D049452:Green Fluorescent Proteins; D004247:DNA; D004996:Ethidium