Conformation urea transition

NEMO has demonstrated its ability to describe accurately both inter- and intramolecular interactions in small systems, including glycine dipeptide conformation profiles, ion-water droplets, and urea transition from nonpla-nar to planar conformation in water. Its applicability to biomacromolecules is not yet known. 

Direct experimental evidence for the existence of an ordered conformation of sugar nucleotides in solutions has been reported by Hirano,344 who observed characteristic optical-rotatory changes for a series of these compounds upon transition from water to concentrated urea solutions. The structural requirements for such an ordered conformation are still not clear. However, data at this point, based on indirect kinetic evidence from hydrogenation and hydroxylamin-olysis reactions (see Section IV, p. 360), seem to accord with the hypothetical model just described. Further studies on the conformations of sugar nucleotides in solution are highly desirable. 

Workers at DuPont used a pharmacophore model and database search to develop the first type III mimetic inhibitor of HIV protease, DuP450 (87)(Fig. 15.38). This evolved from a 3D pharnacophorethat retained two key interactions replacement of the flap-bound water and a hydroxyl transition-state isostere (155). Molecular modeling led to a cyclohexanone as a better spacer between these groups, and finally the seven-membered cyclic urea (87) was created (Fig. 15.38). The development of these inhibitors illustrates the importance of conformational analysis in the design of constrained analogs. 

As stated earlier, proteins can be denatured by heat or by chemical denaturants such as urea or guanidium chloride. For many proteins, a comparison of the degree of unfolding as the concentration of denaturant increases has revealed a relatively sharp transition from the folded, or native, form to the unfolded, or denatured, form, suggesting that only these two conformational states are present to any significant extent (Figure 3.56). A similar sharp transition is observed if one starts with unfolded proteins and removes the denaturants, allowing the proteins to fold. 

Dubin P, Strauss UP. Conformational transitions of hydrophobic polyacids in denaturant solutions. The effect of urea. J Phys Chem 1973 77 1427-1431. 

In contrast, however, we have demonstrated that the macromolecular conformation of the zymogen differs markedly from that of the enzyme (17). Thus, if pepsinogen is transferred from an aqueous solution to concentrated urea, the specific rotation, [a]m, decreases from —200° to —320° in the concentration range of 1.5 to 4.0M urea, and the rotatory dispersion constant, Xc, decreases from 236 to 216 m/z. As shown in Figure 2, which also includes the results obtained with pepsin, this change reflects a configurational transition, similar in sharpness to the transition from an a-... 

Denaturation of ovalbumin by urea or GuCl was long considered to show several kinetic steps and poor reversibility [177-178]. Microheterogeneity had been suspected to be the cause [177] this was confirmed later, when GuCl denaturation of the purified variant of ovalbumin containing two phosphate groups (the major constituent) was shown to conform to the classical two-state reversible transition process [179]. 

The similar observations of the sodium hydroxide concentration dependencies of the peak positions, relative peak intensities, and line-widths of schizophyllan revealed that, like lentinan, its molecule adopted single-helical conformation at lower NaOH concentrations (<0.13 N), while the transition to the random-coil state took place at 0.19 N. Grifolan produced soft gel at neutral pH whose NMR spectrum was similar to those of lentinan and schizophyllan [42]. However, different preparations of grifolan possessed two kinds of solid-state structure and formed different gel types that were described as a helix type (similar to that of lentinan) and a native type that had different structure. Both structures were investigated by NMR spectroscopy, the accent being made on the differences in gel-to-sol transitions induced by addition of alkali, DMSO or urea [86]. 

Elizabe. L. Yeo. L. Harris. K.D.M. Sankar. G. Thomas. J.M. Conformational properties of guest molecules in constrained solid-state environments Bromine K-edge x-ray absorption spectroscopy of 2-bromoalkane/urea inclusion compounds. Chem. Mater. 1998, 10. 1220. Shang, Q. Y., Dou, X. Hudson, B.S. Off-axis orientation of the electronic transition moment for a linear conjugated polyene. Nature 1991, 352. 703. 

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