Biophysical properties

In order to accomplish these diverse physiological tasks described above, nature has created at least five different types of Ca2+ channels. These are termed L-, N-, P/Q-, R-, and T-type. Although they are all structurally similar (Fig. 1) they differ with respect to their biophysical properties. Some of them need only weak depolarizations to open and inactivate fast (e.g., T-type Ca2+ channels), whereas others require strong depolarizations and inactivate more slowly (e.g. P- or L-type Ca2+ channels). Channel types also differ with respect to their sensitivity to drugs. This selectivity is exploited for pharmacotherapy. 

The newest molecular addition to Cl- channels are bestrophins [5]. There are four different bestrophin isoforms in humans. Mutations in Bestl cause Best macular dystrophy, hence their name. All four isoforms induce chloride currents when expressed heterologously. Although they show a dependence on intracellular calcium, their biophysical properties differ from Ca-activated chloride currents typically observed in native cells. Mutagenesis experiments changed the activation of currents and induced slight changes in ion selectivity, lending support to the hypothesis that bestrophins themselves are Cl- channels. 

Table Hydrodynamic techniques for characterising the biophysical properties of polysaccharides in solution ...

There have been considerable efforts toward modeling ADME/Tox properties and the biophysical properties of molecules (see chapters 18-20, 22, 28), including numerous commercial software solutions. Simulations Plus (http //www.simulations-plus.com/) have developed GastroPlus, a product... 

Anatoxin-a has already proven its usefulness as a research tool in our laboratories. It is facilitating the understanding of the biophysical properties of the AChR and of the localization of the AChR in the CNS. The toxin or derivatives of it could be useful therapeutically in diseases of nicotinic receptor pathology (myasthenia gravis or Alzheimer s disease), because as a secondary amine (+)-anatoxin-a can penetrate into the CNS. 

Given that the pharmacological and biophysical properties of recombinant GABAa receptors have been shown to depend critically on their subunit composition, much effort has been directed towards understanding the assembly of native receptors. This could provide a rational basis for the design of compounds able to interact with specific... 

Structure and biophysical properties of cloned voltage-gated channels... 

The intent of this chapter is to establish a comprehensive framework in which the physicochemical properties of permeant molecules, hydrodynamic factors, and mass transport barrier properties of the transcellular and paracellular routes comprising the cell monolayer and the microporous filter support are quantitatively and mechanistically interrelated. We specifically define and quantify the biophysical properties of the paracellular route with the aid of selective hydrophilic permeants that vary in molecular size and charge (neutral, cationic, anionic, and zwitterionic). Further, the quantitative interrelationships of pH, pKa, partition... 

Tomoaia-Cotisel M and Quinn PJ. 1998. Biophysical properties of carotenoids. Subcellular Biochemistry 30 219-242. 

Demchenko AP, Mely Y, Duportail G, Klymchenko AS (2009) Monitoring biophysical properties of lipid membranes by environment-sensitive fluorescent probes. Biophys J 96 3461-3470... 

The advantage of the patch-clamp technique for recording from single levamisole receptors is that biophysical properties of individual receptors... 

Abstract The interplay between three disciplines, organic synthesis, biophysics and cell biology in the study of protein lipidation and its relevance to targeting proteins towards the plasma membrane of cells in precise molecular detail is described in this concept. This interplay is highlighted using the Ras protein as a representative example. Included herein is the development of methods for the synthesis of Ras-derived peptides and fully functional Ras proteins, the determination of the biophysical properties, in... 

Synthetic Lipidated Peptides and Proteins Biophysical Properties... 

Tab. 5.2 Commonly used detergents for work with micelles including some important biophysical properties...

Vidal D, Thormann M, Pons M (2005) LINGO, an efficient holographic text based method to calculate biophysical properties and intermolecular similarities. J. Chem. Inf. Model. 45 386-393. 

Despite the fact that many different cationic lipids have been synthesized and tested for transfection (25 34), relatively few systematic structure activity TE-relationship studies have been performed (35 39). As a result, no general relationship between chemical structure and TE could be drawn from these studies. One reason for this is that the chemical structure of a cationic lipid is not directly responsible for TE. TE rather depends on the biophysical characteristics of the cationic lipid aggregate (e.g., liposomes and lipoplexes), which, for its part, is dependent on the chemical structure of the lipids. In a previous study with analogs of the transfection lipid A-[l-(2,3-dioleoyloxy) propyl]-A,A,A-trimethylammoniumchloride (DOTAP) (40) which differ in their nonpolar hydrocarbon chains, it could be shown that the TE strongly depended on the biophysical properties of the resulting liposomes and lipoplexes (35). Minimal alterations of biophysical properties by using lipids with different hydrocarbon chains or by mixing the lipid with different neutral helper lipids could completely allow or prevent transfection. 

Wolfert MA, Dash PR, Nazarova O, et al. Polyelectrolyte vectors for gene delivery influence of cationic polymer on biophysical properties of complexes formed with DNA. Bioconjug Chem 1999 10(6) 993-1004. 

Channels Transmembrane pores selectivity for solutes depends on biophysical properties that are actively regulated... 

Biophysical properties such as high thermal stability are thus of paramount importance in the decision as to whether or not these molecules are useful in vivo. The above described approaches may provide a strategy to meet these requirements and may eventually result in attractive modalities for the targeting of solid tumours in patients. 

To seek compounds with optimal characteristics for external and internal transfer on a rational basis requires an understanding of pesticide availance and how this is influenced by physico-chemical and biophysical properties to predict the most effective compounds then requires a knowledge of the relationship between these properties and molecular structure. This paper briefly reviews the considerable progress which has been made in these directions and the prospects for future advance. 

---