Conformational changes in aqueous solutions

Similarly mono-(o-hydroxyphenyl)triphenylporphyrin (65) was covalently attached to a cyclodextrin unit, in the hope of preparing a water-soluble oxygen carrying model While 123 did not display the desired properties, guest inclusion in the cyclodextrin moiety appears to induce novel conformational changes in aqueous solutions. 

Polyelectrolyte Samples and Their Conformational Changes in Aqueous Solutions... 

Hydration of a neutral polymer can roughly be classified into two categories direct hydrogen bonds (referred to as H-bonds) between a polymer chain and water molecules (p-w), and the hydrophobic hydration of water molecules surrounding a hydrophobic group on a chain in a cage structure by water-water (w-w) H-bonds. In this section, we extend the combinatorial method for the partition function presented in the previous section to suit for the problem of solvent adsorption, and study polymer conformation change in aqueous solutions due to the direct p-w H-bonds. 

The studies summarized in this section have proved particularly valuable, because they were conducted in (mostly aqueous) solution, enabling comparison with X-ray or neutron diffraction studies, for which crystalline material must be used. Although the conformation of a crystalline protein can be essentially the same as that in aqueous solution, it is not necessarily correct to make this assumption, since there may be large conformational changes in such solution, contingent on the variables of protein concentration, pH, ionic strength, and temperature. 

The titration curves of polyacids which undergo a conformational transition in aqueous solution greatly differ from those of polyacids without transition. A discontinuous change of pK vs the degree of ionization (a) is observed in the former case which can be related to a transition from a rather compact state to a mean extended conformation in the latter case, a gradual increase in the electric potential is observed in accordance with the absence of any special conformation. The cases of PM A and PAA clearly show such features although in our opinion PMA is a limiting case. 

Fig. 4. Conformational equilibria in aqueous solution and guest-induced conformational change of chromophore-modified cyclodextrins (a) larger guest, (b) smaller guest.

The second application of the CFTI protocol is the evaluation of the free energy differences between four states of the linear form of the opioid peptide DPDPE in solution. Our primary result is the determination of the free energy differences between the representative stable structures j3c and Pe and the cyclic-like conformer Cyc of linear DPDPE in aqueous solution. These free energy differences, 4.0 kcal/mol between pc and Cyc, and 6.3 kcal/mol between pE and Cyc, reflect the cost of pre-organizing the linear peptide into a conformation conducive for disulfide bond formation. Such a conformational change is a pre-requisite for the chemical reaction of S-S bond formation to proceed. The predicted low population of the cyclic-like structure, which is presumably the biologically active conformer, agrees qualitatively with observed lower potency and different receptor specificity of the linear form relative to the cyclic peptide. 

As a result of the micellar environment, enzymes and proteins acquire novel conformational and/or dynamic properties, which has led to an interesting research perspective from both the biophysical and the biotechnological points of view [173-175], From the comparison of some properties of catalase and horseradish peroxidase solubilized in wa-ter/AOT/n-heptane microemulsions with those in an aqueous solution of AOT it was ascertained that the secondary structure of catalase significantly changes in the presence of an aqueous micellar solution of AOT, whereas in AOT/n-heptane reverse micelles it does not change. On the other hand, AOT has no effect on horseradish peroxidase in aqueous solution, whereas slight changes in the secondary structure of horseradish peroxidase in AOT/n-heptane reverse micelles occur [176],... 

It is important to note that most molecules are not rigid but may prefer a distrinct structure and the conformation of a molecule strongly depends on its specific environment. Hence, the crystal structure of a drug does not have to correspond to the receptor bound conformation. Also, a conformation in solution depends on the nature of the solvent and measuring conditions, and may change when the molecule is bound to the receptor [4]. In addition, different receptors or receptor subtypes can bind the same drug in different conformations. It is a general assumption and observation, but by far not a strict condition, that the conformation in aqueous solution is similar to the bound conformation and is a better representation of the bioactive conformation than an X-ray structure of the isolated molecule in the crystalline state. 

In 1958 Sarda and Desnuelle [79] discovered the lipase activation at the interfaces. They observed that porcine pancreatic lipase in aqueous solution was activated some 10-fold at hydrophobic interfaces which were created by poorly water-soluble substrates. An artificial interface created in the presence of organic solvent can also increase the activity of the lipase. This interfacial activation was hypothesized to be due to a dehydration of the ester substrate at the interface [80], or enzyme conformational change resulting from the adsorption of the lipase onto a hydrophobic interface [42,81,82]. 

In the case of 2-hydroxytetrahydropyran, the axial conformer 22 is calculated to be more stable than its equatorial conformer 23 in vacuum (Fig. 12). Solvent effects change the equilibrium constant and the equatorial form 23 is favored in aqueous solution, in agreement with data. The magnitude of the conformational endo-anomeric effect in 22 is estimated to 2.0 kcal/mol (gas phase stereoelectronic effects overwhelming the steric... 

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