Structure/Function Analysis of Peptoid/Lipitoid:DNA Complexes

• Published in: Journal of pharmaceutical sciences Vol. 92; no. 9; pp. 1905 - 1918
• Main Authors: Lobo, Brian A., Vetro, Joseph A., Suich, Daniel M., Zuckermann, Ronald N., Middaugh, C.Russell
• Format: Journal Article
• Language: English
• Published: Hoboken Elsevier Inc 01.09.2003; Wiley Subscription Services, Inc., A Wiley Company; Wiley; American Pharmaceutical Association
• Subjects: Animals; Biological and medical sciences; Chemical Phenomena; Chemistry, Physical; CHO Cells; Circular Dichroism; COS Cells; Cricetinae; DNA - administration & dosage; DNA - chemistry; Drug Carriers; Ethidium - chemistry; Gene Transfer Techniques; General pharmacology; Green Fluorescent Proteins; Humans; Luminescent Proteins - biosynthesis; Luminescent Proteins - genetics; Medical sciences; Nucleic Acid Conformation; Particle Size; peptoid/lipitoid:DNA complexes; Peptoids - chemistry; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Phospholipids - chemistry; Spectroscopy, Fourier Transform Infrared; structure/function analysis; Transfection; peptoid/lipitoid:DNA complexes; structure/function analysis; Complexation; Particle size; Pharmaceutical technology; Peptides; Phospholipid; Lipids; In vitro; Structure function relationship; Genetic transfer; Transfection; DNA; Conjugated compound; Surface potential
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.10450

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, ζ-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. © 2003 Wiley-Liss, Inc. and the American Pharmacists Association.