Hydrophilic folding

Of particular interest when considering ionizable compounds is the difference of lipophilicity between the neutral species and one of its ionic forms, because ionization dramatically alters intramolecular interactions (such as electronic conjugation, internal ionic and hydrogen bonds, polarity, hydrophilic folding, and shielding). In a given solvent system, diff (log is approximately constant for compounds with similar chemical... 

As a result of hydrophobic and/or hydrophilic folding, a solute may become more polar in polar solvents and more lipophilic in nonpolar solvents. In effect, such a solute to some extent adapts its lipophilicity to that of the medium, thereby behaving analogously to a chameleon, which changes color to resemble that of the environment. > ... 

The pharmacokinetics of flexible drug molecules is markedly influenced by their conformational behavior. As mentioned earlier, flexible compounds with suitable moieties may exhibit hydrophobic collapse in polar solvents, and hydrophilic folding in nonpolar environments." It is postulated that these... 

The sequence space of proteins is extremely dense. The number of possible protein sequences is 20. It is clear that even by the fastest combinatorial procedure only a very small fraction of such sequences could have been synthesized. Of course, not all of these sequences will encode protein stmctures which for functional purjDoses are constrained to have certain characteristics. A natural question that arises is how do viable protein stmctures emerge from the vast sea of sequence space The two physical features of folded stmctures are (l)in general native proteins are compact but not maximally so. (2) The dense interior of proteins is largely made up of hydrophobic residues and the hydrophilic residues are better accommodated on the surface. These characteristics give the folded stmctures a lower free energy in comparison to all other confonnations. 

Simplified models for proteins are being used to predict their stmcture and the folding process. One is the lattice model where proteins are represented as self-avoiding flexible chains on lattices, and the lattice sites are occupied by the different residues (29). When only hydrophobic interactions are considered and the residues are either hydrophobic or hydrophilic, simulations have shown that, as in proteins, the stmctures with optimum energy are compact and few in number. An additional component, hydrogen bonding, has to be invoked to obtain stmctures similar to the secondary stmctures observed in nature (30). 

We thus have here a case where a mutation on the surface of the globin fold, replacing a hydrophilic residue with a hydrophobic one, changes important properties of the molecule and produces a lethal disease. Why has the... 

Hydrophilic liquids can also cause stabilization and amplification of fluorescence Thus, Dunphy et al employed water or ethanol vapor to intensify the emissions of their chromatograms after treatment with 2, 7 dichlorofluorescein [260] Some groups of workers have pointed out that the layer matenal itself can affect the yield of fluorescent energy [261 —263] Thus, polyamide and cellulose layers were employed m addition to silica gel ones [245] The fluorescence yield was generally increased by a factor of 5 to 10 [264], but the increase can reach 100-fold [234, 265]... 

Deactivation generally refers to a change in the physical structure of the enzyme, often caused by an increase in temperature. Some of the amino acids in a protein chain are hydrophobic. Others are hydrophilic. Proteins in solution fold into elaborate but characteristic shapes to increase like-to-like interactions... 

Proteins derive their powerful and diverse capacity for molecular recognition and catalysis from their ability to fold into defined secondary and tertiary structures and display specific functional groups at precise locations in space. Functional protein domains are typically 50-200 residues in length and utilize a specific sequence of side chains to encode folded structures that have a compact hydrophobic core and a hydrophilic surface. Mimicry of protein structure and function by non-natural ohgomers such as peptoids wiU not only require the synthesis of >50mers with a variety of side chains, but wiU also require these non-natural sequences to adopt, in water, tertiary structures that are rich in secondary structure. 

In order for folded helices to assemble into tertiary structures in water, they need to be amphipathic (e.g. where one hehcal face is hydrophobic and the other is hydrophilic). Because the first hehcal peptoids contained very hydrophobic chiral residues, ways to increase the water solubihty and side-chain diversity of the hehx-indudng residues were investigated [49]. It was found that a series of side chains with chiral-substituted carboxamides in place of the aromatic group could stiU favor hehx formation, while dramatically increasing water solubility. 

Evidence exists that the relative solubility of amines and inhibitors in heterogeneous oil-water systems could be decisive in formation of nitrosamines and blocking these reactions, Nitrosopyrrolidine formation in bacon predominates in the adipose tissue despite the fact that its precursor, proline, predominates in the lean tissue (5,6,7). Mottram and Patterson (8) partly attribute this phenomenon to the fact that the adipose tissue furnishes a medium in which nitrosation is favored, Massey, et al, (9) found that the presence of decane in a model heterogeneous system caused a 20-fold increase in rate of nitrosamine formation from lipophilic dihexylamine, but had no effect on nitrosation of hydrophilic pyrrolidine. Ascorbic acid in the presence of decane enhanced the synthesis of nitrosamines from lipophilic amines, but had no effect on nitrosation of pyrrolidine. The oil-soluble inhibitor ascorbyl palmitate had little influence on the formation of nitrosamines in the presence or absence of decane. 

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