Lipids, cationic multivalent

Bilayer phase transitions are sensitive to the presence of solutes that interact with lipids, including multivalent cations, lipid-soluble agents, peptides, and proteins. 

With respect to the carrier mechanism, the phenomenology of the carrier transport of ions is discussed in terms of the criteria and kinetic scheme for the carrier mechanism the molecular structure of the Valinomycin-potassium ion complex is considered in terms of the polar core wherein the ion resides and comparison is made to the Enniatin B complexation of ions it is seen again that anion vs cation selectivity is the result of chemical structure and conformation lipid proximity and polar component of the polar core are discussed relative to monovalent vs multivalent cation selectivity and the dramatic monovalent cation selectivity of Valinomycin is demonstrated to be the result of the conformational energetics of forming polar cores of sizes suitable for different sized monovalent cations. 

It has been known for some years that gramicidin forms transmembrane ion channels in lipid bilayers and biological membranes and that these channels are assembled from two molecules of the polypeptide 213). The channels are permeable specifically to small monovalent cations [such as H+, Na+, K+, Rb+, Cs+, Tl+, NH4+, CHjNHj, but not (CH3)2NH2+J and small neutral molecules (such as water, but not urea). They do not allow passage of anions or multivalent cations 21 n. 

Keywords Cholesterol Gene delivery Multivalent cationic lipid siRNA Small... 

Highly Charged Multivalent Cationic Lipids with Dendritic Headgroups Promote... 

In this chapter, we provide an overview of our recent efforts to develop a fundamental science base for the design and preparation of optimal lipid-based carriers of DNA and siRNA for gene therapy and gene silencing. We employ synthesis of custom multivalent lipids, synchrotron X-ray diffraction (XRD) techniques, optical and cryo-electron microscopy, as well as biological assays in order to correlate the structures, chemical, and biophysical properties of cationic liposome (CL)-NA complexes to their biological activity and to clarify the interactions between CL-NA complexes and cellular components. Earlier work has been reviewed elsewhere [1-7] and will not be covered exhaustively here. 

Hnc phase, while the formation of micelles in the HjC phase is driven by a highly charged (16+), cone-shaped multivalent cationic lipid. 

The internal structure of the complexes can directly determine the mechanism of transfection [4, 23, 25]. We have found that for Lac CL-DNA complexes, the membrane charge density (aM) is a predictive parameter for transfection efficiency [21] (see Sect. 2), i.e., the data for monovalent and multivalent cationic lipids are described by a simple bell-curve. In contrast, for inverted hexagonal HnC CL-DNA complexes, TE is independent of aM, suggesting a distinctly different mechanism of transfection. Consistent with the TE data, confocal microscopy revealed distinctly different CL-DNA complex pathways and interactions with cells, which depended on both the structure (HnC vs Lac) and, for Lr/ complexes, on aM [25]. Thus, the mechanism of transfection by CL-DNA complexes is dependent both on their structure and, for a given structure, on chemical and physical parameters of the complexes. 

We have mapped the transfection efficiency of DL/DOPC-DNA complexes as a function of molar fraction of DL (cPDL) and the cationic lipid/DNA charge ratio (Pchg)- As observed for DOTAP and multivalent lipids with valencies up to +5, TE... 

In addition, for CL-siRNA complexes, further exploration of the relationships between cationic lipid valence, complex stability, silencing efficiency, and cytotoxicity with a series of multivalent lipids such as the MVLS or DLs is a logical next step. 

Ewert K, Ahmad A, Evans HM, Schmidt H-W, Safinya CR (2002) Efficient synthesis and cell-transfection properties of a new multivalent cationic lipid for non-viral gene delivery. J Med Chem 45 5023-5029... 

Farago O, Ewert KK, Ahmad A, Evans HM, Grpnbech-Jensen N, Safinya CR (2008) Transitions between distinct compaction regimes in complexes of multivalent cationic lipids and DNA. Biophys J 95 836-846... 

Duzgnues, N., Goldstwin, J. A., Friend, D. S., and Feigner, P. L. Fusion of liposomes containing a novel cationic lipid, V-[2,3-(dioleoyoxy)-propyl]-lV,lV,lV-trimethylam-monium Induction by multivalent anions and asymmetric fusion with acidic phospholipid vesicles. Biochemistry 28 9179—9184, 1989. 

L. J. McDonald and M. D. Mamrack, Phosphoinositide hydrolysis by phospholipase C modulated by multivalent cations La3 +, A13 +, neomycin, polyamines, and melittin, J. Lipid Medial Cell Signal, 11 (1995) 81-91. 

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