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Polar Head Group (polar + head_group)
Selected AbstractsPolymeric alkenoxy amino acid surfactants: I. Highly selective class of molecular micelles for chiral separation of ,-blockersELECTROPHORESIS, Issue 15 2003Syed A. A. Rizvi Abstract Two amino acid-based alkenoxy micelle polymers were synthesized for this study. These include polysodium N -undecenoxy carbonyl- L -leucinate (poly- L -SUCL) and polysodium N -undecenoxy carbonyl- L -isoleucinate (poly- L -SUCIL). The polymerization time and concentration of the synthesized micelle polymers were optimized by 1H-nuclear magnetic resonance (NMR) and capillary electrophoresis (CE) experiments. Detailed physicochemical properties (1H NMR, critical micelle concentration (CMC), optical rotation, partial specific volume, aggregation number, and polarity) were determined, and these molecular micelles were introduced as a pseudostationary phase in micellar electrokinetic chromatography to study the molecular recognition and to develop a method for simultaneous separation of eight chiral ,-blockers. It is found that poly- L -SUCL gives overall better chiral resolution and wider chiral window than poly- L -SUCIL. After optimizing the type of micelle polymer, injection size and temperature, simultaneous separation and enantioseparation of eight ,-blockers were achieved in less than 35 min. A comparison with the amide-type surfactants of the same polar head group and alkyl chain length showed that carbamate-type surfactants always work better than the corresponding amide-type surfactant. [source] Structure,activity relationships for acute and chronic toxicity of alcohol ether sulfatesENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2000Scott D. Dyer Abstract Acoholethersulfates(AES)areanionicsurfactantscommonlyusedinconsumerproducts. Commercial AES alkyl chain lengths range from C12 to C18, with ethoxylate (EO) units ranging from 1 to 5. Alkyl sulfate is a special case of AES with no EO units. Acute and chronic toxicity tests using Ceriodaphnia dubia via a novel flowthrough method were conducted with 18 AES compounds to derive SARs for effects assessment. In general, acute toxicity (48-h LC50) increased with increased alkyl carbon chain length and decreased with increased numbers of EO units. Parabolic structure,chronic (7-d) toxicity relationships were observed for endpoints such as the no-observed-effect concentration, lowest-observed-effect concentration, maximum acceptable toxicant concentration, EC20, and EC50. A linear relationship of the fractional negative-charged surface area (FNSA-3) with acute toxicity was also determined. FNSA-3 refers primarily to the polar head group of AES and secondarily to the alkyl chain. Seventy percent of the variance in the chronic data was addressed with a quadratic equation relating toxicity to alkyl chain length and EO units. Alternatively, the molecular descriptors FNSA-3 and S3P (3,p, which is the simple, third-order path index) were also found to address most of the data nonlinearity. A chronic test conducted with a mixture of four AES components indicated additivity, leading to the support of the performance of an effects assessment of AES as a mixture. [source] PDK1 and PKB/Akt: Ideal Targets for Development of New Strategies to Structure-Based Drug DesignIUBMB LIFE, Issue 3 2003Thomas Harris Abstract Growth factor binding events to receptor tyrosine kinases result in activation of phosphatidylinositol 3-kinase (PI3K), and activated PI3K generates the membrane-bound second messengers phosphatidylinositol 3,4-diphosphate [PI(3,4)P2] and PI(3,4,5)P3, which mediate membrane translocation of the phosphoinositide-dependent kinase-1 (PDK1) and protein kinase B (PKB, also known as Akt). In addition to the kinase domain, PDK1 and PKB contain a pleckstrin homology (PH) domain that binds to the second messenger, resulting in the phosphorylation and activation of PKB by PDK1. Recent evidence indicates that constitutive activation of PKB contributes to cancer progression by promoting proliferation and increased cell survival. The indicating of PDK1 and PKB as primary targets for discovery of anticancer drugs, together with the observations that both PDK1 and PKB contain small-molecule regulatory binding sites that may be in proximity to the kinase active site, make PDK1 and PKB ideal targets for the development of new strategies to structure-based drug design. While X-ray structures have been reported for the kinase domains of PDK1 and PKB, no suitable crystals have been obtained for either PDK1 or PKB with their PH domains intact. In this regard, a novel structure-based strategy is proposed, which utilizes segmental isotopic labeling of the PH domain in combination with site-directed spin labeling of the kinase active site. Then, long-range distance restraints between the 15N-labeled backbone amide groups of the PH domain and the unpaired electron of the active site spin label can be determined from magnetic resonance studies of the enhancement effect that the paramagnetic spin label has on the nuclear relaxation rates of the amide protons. The determination of the structure and position of the PH domain with respect to the known X-ray structure of the kinase active site could be useful in the rational design of potent and selective inhibitors of PDK1 and PKB by 'linking' the free energies of binding of substrate (ATP) analogs with analogs of the inositol polar head group of the phospholipid second messenger. The combined use of X-ray crystallography, segmental isotopic and spin labeling, and magnetic resonance studies can be further extended to the study of other dynamic multidomain proteins and targets for structure-based drug design. IUBMB Life, 55: 117-126, 2003 [source] Mechanistic studies of branched-chain alkanols as skin permeation enhancersJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 3 2004Doungdaw Chantasart Abstract As part of a long-term effort to understand the structure/function relationship between chemical permeation enhancers and skin permeation enhancement, the present study examined the influence of hydrocarbon chain branching on the effectiveness of skin permeation enhancers of the type that possesses a polar group (e.g., the hydroxyl group) attached to a hydrocarbon chain(s). The effects of x -hexanol, x -heptanol, x -octanol, and x -nonanol (where x is the position of the hydroxyl group ranging from 1 up to 5) on the transport of a probe permeant, corticosterone, across hairless mouse skin (HMS) were investigated. Isoenhancement concentrations are defined as the aqueous concentrations for which different enhancers induce the same extent of permeant transport enhancement, E, across the lipoidal pathway of stratum corneum (SC). The isoenhancement concentrations of 2-alkanol, 3-alkanol, 4-alkanol, and 5-alkanol to induce E,=,10 were approximately 1.9-, 2.6-, 3.1-, and 3.9-fold higher, respectively, than those of the 1-alkanols of the same molecular formula. This suggested that the branched-chain alkanols have lower enhancer potency than the 1-alkanols of the same molecular formula; the potency decreases as the hydroxyl group moves from the end of the chain towards the center of the enhancer alkyl chain. To further investigate the mechanism(s) of action of the branched-chain alkanols as skin permeation enhancers, the equilibrium uptake of the enhancers into the hairless mouse skin stratum corneum (HMS SC) from aqueous enhancer solutions of E,=,10 was determined. The data from these experiments provided a direct measure of the "intrinsic" potency of the enhancer. In the same experiments, the equilibrium partitioning (distribution) of a surrogate permeant, estradiol (E2,), into the HMS SC was also determined and compared to the partitioning from PBS (no enhancer present). The uptake amounts (micromole/mg SC) for 1-alkanols into the intercellular lipids of the SC were found to be essentially the same at their isoenhancement concentrations. However, at their isoenhancement concentrations, the uptake amounts of the branched-chain alkanols into the intercellular lipids of HMS SC were higher than those of the 1-alkanols. These results support the view that: (1) the intrinsic potencies of the 1-alkanols are essentially the same and independent of their 1-alkyl chain length at their isoenhancement concentrations, (2) the intrinsic potencies of the branched-chain alkanols are lower than those of the normal alkanols, and (3) branching of the alkyl chain reduces the ability of the enhancer to effect lipid fluidization in the SC lipid lamellae at the target site(s). The enhancement effects of the branched-chain alkanols and the 1-alkanols at their isoenhancement concentrations upon E2, partitioning into the SC intercellular lipids were found to be approximately the same and in the range of five- to eight-fold enhancement. The constancy of this enhancement for E2, partitioning suggests that the mechanism of enhancement action for the branched-chain alkanols and the 1-alkanols are the same. Additionally, a good correlation of the intercellular lipid/PBS partition coefficients of both the branched-chain alkanols and the 1-alkanols with the n -octanol/PBS partition coefficients was found. This supports the view that the chemical microenvironment of the polar head group and the alkyl group of the studied enhancers at the site of skin permeation enhancer action in the SC lipid lamellae can be represented by water-saturated n -octanol for both the branched-chain alkanols and the 1-alkanols. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:762,779, 2004 [source] Influences of alkyl group chain length and polar head group on chemical skin permeation enhancementJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 8 2001Kevin S. Warner Abstract Previous investigations in our laboratory on the influence of the n -alkanols and the 1-alkyl-2-pyrrolidones as skin permeation enhancers for steroid molecules as permeants demonstrated that the enhancer potencies (based on aqueous concentration values) of these two homologous series were the same when compared at the same alkyl chain length; that is, the contribution of the hydroxyl group and that of the pyrrolidone group to enhancer potency were the same. The purpose of the present study was to further investigate what was believed to be a somewhat surprising finding, and two additional homologous series, the 1,2-alkanediols and N,N -dimethylalkanamides, were selected for study as enhancers. Corticosterone (CS) flux enhancement along the lipoidal pathway of hairless mouse skin stratum corneum was determined with 1,2-hexane-, 1,2-octane-, and 1,2-decanediol and with N,N -dimethylhexanamide, N,N - dimethylheptanamide, N,N -dimethyloctanamide, and N,N -dimethylnonanamide as enhancers. The enhancement factor (E) for the lipoidal pathway was calculated from the CS permeability coefficient and the CS solubility data over a 4 to 100 range of E values. Comparisons of the enhancer potencies of all four homologous series revealed that the enhancer potencies of all were very nearly the same when compared at equal alkyl group chain length. Moreover, the contribution of each of the polar head groups toward the enhancer potency was essentially constant, independent of the alkyl group chain length. It was reasoned that this outcome was either the result of the random selection of four polar head groups making the same contribution to enhancer potency or the result of these particular polar head groups not contributing to enhancer potency. To test the hypothesis that the former was more likely than the latter and that a suitable semipolar organic phase may mimic the microenvironment of the polar head group at the site of enhancer action, n -octanol,phosphate buffered saline (PBS) and n -hexane,PBS partition coefficients were determined for all the enhancers. The n -octanol,PBS partition coefficients for the enhancers, but not the n -hexane,PBS partition coefficients, were very nearly the same when compared at equal alkyl group chain lengths; this result supports the hypothesis that each of the four polar head groups likely contributes the same toward the enhancer potency and locates in the semipolar region of the hairless mouse skin stratum corneum lipid bilayers, which is well-approximated by water-saturated n -octanol. © 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:1143,1153, 2001 [source] Collision-induced dissociation of glycero phospholipids using electrospray ion-trap mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 24 2001Åsmund Larsen Characterisation of phospholipids was achieved using collision-induced dissociation (CID) with an ion-trap mass spectrometer. The product ions were compared with those obtained with a triple quadrupole mass spectrometer. In the negative ion mode the product ions were mainly sn -1 and sn -2 lyso-phospholipids with neutral loss of ketene in combination with neutral loss of the polar head group. Less abundant product ions were sn -1 and sn -2 carboxylate anions. CID using a triple quadrupole mass spectrometer, however, gave primarily the sn -1 and sn -2 carboxylate anions together with lyso-phosphatidic acid with neutral loss of water. For the ion trap a charge-remote-type mechanism is proposed for formation of the lyso-phospholipid product ions by loss of ,-hydrogen on the fatty acid moiety, electron rearrangement and neutral loss of ketene. A second mechanism involves nucleophilic attack of the phosphate oxygen on the sn -1 and sn -2 glycerol backbone to form carboxylate anions with neutral loss of cyclo lyso-phospholipids. CID (MS3 and MS4) of the lyso-phospholipids using the ion-trap gave the same carboxylate anions as those obtained with a triple quadrupole instrument where multiple collisions in the collision cell are expected to occur. The data demonstrate that phospholipid species determination can be performed by using LC/MSn with an ion-trap mass spectrometer with detection of the lyso-phospholipid anions. The ion-trap showed no loss in sensitivity in full scan MSn compared to multiple reaction monitoring data acquisition. In combination with on-line liquid chromatography this feature makes the ion-trap useful in the scanning modes for rapid screening of low concentrations of phospholipid species in biological samples as recently described (Uran S, Larsen,Å, Jacobsen PB, Skotland T. J. Chromatogr. B 2001; 758: 265). Copyright © 2001 John Wiley & Sons, Ltd. [source] The immediate-early oncoproteins Fra-1, c-Fos, and c-Jun have distinguishable surface behavior and interactions with phospholipidsBIOPOLYMERS, Issue 9 2009Marķa Cecilia Gaggiotti Abstract This work explores the surface properties of the transcription factor Fra-1 and compares them with those of two other immediate early proteins, c-Fos and c-Jun, to establish generalities and differences in the surface behavior and interaction with phospholipids of this type of proteins. We present several experimental clues of the flexible nature of Fra-1, c-Fos, and c-Jun that support sequence-based predictions of their intrinsical disorder. The values of surface parameters for Fra-1 are similar in general to those of c-Fos and c-Jun. However, we find differences in the interactions of the three proteins with phospholipids. The closely related Fra-1 and c-Fos share affinity for anionic lipids but the former has more affinity for a condensed phase and senses a change in DPPC phase, while the latter has more affinity for an expanded phase. These features are in contrast with our previous finding that c-Jun is not selective for phospholipid polar head group or charge. We show here that at least some immediate early transcription factors can interact with membrane phospholipids in a distinguishable manner, and this shall provide a basis for their potential capacity to regulate membrane-mediated cellular processes. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 710,718, 2009. This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com [source] | |||||||||||||