Hydrophobic centers

ATPase [46,48] pharmacophoric elements H-bond acceptor group and two hydrophobic centers ... 

Another approach consists of identifying chemical pharmacophore features that interact directly with the bound ligand. They can be summarized as hydrophobic centers, H-bond donors and acceptors, positive and negative charges, aromatic centers, etc. These surface... 

Integral membrane proteins are partially embedded in the hydrophobic center of the lipid bilayer. 

The answer is E. Anesthetics are highly lipid-soluble and experiments with isolated membranes indicate that these molecules can dissolve in the hydrophobic center of the membrane bilayer. This causes a measurable increase in the membrane fluidity by disrupting the packed structure of phospholipids tails. This is considered to be the main, direct mechanism by which this class of drugs inhibits neurotransmission (pain sensations) in neurons. Hallucinogens and opiates may also affect membrane fluidity, but their effects occur by indirect mechanisms, resulting from changes in the protein or lipid composition of the membranes. 

Commelinaceae) shows an extra absorption band at 583 nm at pH values above 4.0, which makes this pigment highly colored at these pH values.The high stability of this type of pigments with as much as four acyl units was assumed to be due to the difficulty of water molecule diffusion to the hydrophobic center formed by the acyl groups and the aglycone. 

Finely divided celluloses may also be used in the column in conjunction with attached hydrophobic groups such as octyl alcohol. In this case, it is proteins with exposed hydrophobic centers that bind to the column with varying affinities. These proteins may be eluted in order of decreasing affinity for the column by increasing the level of free octyl alcohol in the eluting buffer. 

The inhomogeneous structure of a micelle (or inverse micelle) can influence the course of a photoinduced electron transfer. Such a micelle is biphasic, containing a hydrocarbon-like core and a water-like surface. If the photoinduced electron transfer produces a product which has lower solubility in the aqueous phase (a situation which might obtain if a cationic acceptor is reduced to a neutral product), this product will be directed by solubility considerations to move toward the hydrophobic center of the micelle, i.e., remote from the site of the forward electron transfer. This spatial separation, shown conceptually in Scheme 4, in turn will retard the rate of the back reaction compared with that of the forward reaction. 

Figure 13.4 Seven pharmacophore queries. The mesh balls represent H-bond acceptor sites, hydrophobic centers and aromatic centers. The solid white surfaces represent shape constrain. 

Structures for Cy and the molecular complexes have been described many times before [5] and require no repetition here. Suffice it to say that the hydrophobic center of the truncated conical shape of the host is the favored site for interaction with any non-polar group that is part of the guest on molecular association. Hydrophilic groups of the guest are left outside to interact with the... 

Pharmacophore keys are 3-D structural keys that are based on features of a molecule that are thought to have relevance for receptor binding. The features typically include hydrogen bond donors, hydrogen bond acceptors, charged centers, aromatic ring centers and hydrophobic centers. Pharmacophore keys are usually based on combinations of three or four pharmacophoric features and their associated distances. Flexibility can be taken into account by combining the keys for all distinct conformations of a molecule. 

Despite the large variety of molecules recently described as desirable Kvl.5 inhibitors, there has been limited success in predicting ligand-based Kvl.5 pharmacophores. Recently, a pharmacophore model was derived from several members of the bisaryl series (see Table 1) and another series. The model consists of three hydrophobic centers in a triangular arrangement, and it was used to identify anthranilic amides as novel Kvl.5 inhibitors [43]. A similar paucity of published data exists with regard to pharmacophores based on the Kvl.5 channel structure [59]. 

Derivatized cyclodextrins can interact with chiral substances in a number of different ways. If, the positions 2 and 6 are alkylated (pentylated), very dispersive (hydrophobic) centers are introduced that can strongly interact with any alkyl chains contained by the solutes. After pentylation of the 2 and 6 positions has been accomplished, the 3-position hydroxyl group can then be trifluoroacetylated. This stationary phase is widely used and it has been found that the derivatized y-cyclodextrin is more chirally selective than the /3 material. It has been successfully used for the separation of both very small and very large chiral molecules. The cyclodextrin hydroxyl groups can also be made to react with pure S hydroxypropyl groups and then per-... 

Researchers at Aventis described a pharmacophore for Kvl.5 channel blockers consisting of three hydrophobic centers in a triangular arrangement. First observed in an earlier active series [73], the pharmacophore was validated using a database of 423 Kvl.5 blockers [74], The query was able to retrieve 58% of the known actives. A pharmacophore search of the corporate collection identified 27 clusters containing 1975 compounds. Screening the representatives of 18 clusters led to the discovery of an anthranilamide hit molecule (Kvl.5 IC50 = 5.6pM in Xenopus oocytes) [74],... 

Ekins et al. built QSAR models using Catalyst software to rank and predict inhibitors for P-gp substrate transport. In their first attempt, four different pharmacophores were derived from the analysis of inhibitors of digoxin transport, vinblastine binding, or intracellular accumulation of vinblastine and calcein [61]. These data were then combined with experiments using verapamil as inhibitor and led to the construction of a unique pharmacophore consisting of one hydrogen-bond acceptor, one aromatic ring, and two hydrophobic centers [62]. 

Groups with target interaction (i.e., hydrogen bond acceptors, hydrogen bond donors, positively charged centers, aromatic rings, hydrophobic centers) are the pharmacophore centers [66]. 

Five pharmacophore point types are used to generate PDT fingerprints hydrogen-bond acceptor atom, hydrogen-bond donor atom, acceptor site, donor site, and hydrophobic center. While donor and acceptor atoms are part of the molecule, site points refer to interaction points located on a virtual receptor defined by geometrical criteria [Martin, Bures et al., 1993]. Interfeature distances from 2.5 to 15.0 A are divided into 27 distance bins of equal width (i.e.,... 

Homology model based on SPIRO-OXINDOLE and NUTLIN MDM2 structures Constrained search Hydrophobic centers and HBonds (49305)... 

Figure 18-16 depicts a model for the selective uptake of cholesteryl esters by a cell-surface receptor called SR-BI (scavenger receptor, class B, type I). SR-BI binds HDL, LDL, and VLDL and can mediate selective uptake from all of these lipoproteins. The detailed mechanism of selective llpid uptake has not yet been elucidated, but It may entail hemifuslon of the outer phospholipid monolayer of the lipoprotein and the exoplasmic leaflet of the plasma membrane. The cholesteryl esters Initially enter the hydrophobic center of the plasma membrane, are subsequently transferred across the Inner leaflet, and are eventually hydrolyzed by cytosolic, not lysosomal, cholesteryl esterases. The llpid-depleted particles remaining after llpid transfer dissociate from SR-BI and return to the circulation they can then extract more phospholipid and cholesterol from other cells by means of the ABCAl protein or other cell-surface transport proteins (see Figure 18-13c). Eventually, small llpid-depleted HDL particles circulating In the bloodstream are filtered out by the kidney and bind to a different receptor on renal epithelial cells. After these particles have been Internalized by receptor-mediated endocytosis, they are degraded by lysosomes.

The more hydrophobic neutral molecules tend to penetrate the micelle to the hydrophobic center and associate for an equilibrium amount of time. As a result, they are carried along for a short time with the micelle toward the anode. This large molecule lags further behind the main bulk of the system. Different neutral molecules penetrate and associate for various lengths of time. This means that neutral molecules can become separated. This technique has been called micellar electrokinetic capillary chromatography (MECC), Figure 31-8. 

Biochemical reactions take place in the hydrophobic centers of membranes or enzyme clefts. Aqueous compartments of biological cells are usually taboo media for the formation of small molecular assemblies or covalent compounds. There is, however, one notable exception, namely the formation of inclusion... 

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