Conformational constraint

Figure 8 A joint principal coordinate projection of the occupied regions in the conformational spaces of linear (Ala) (triangles) and its conformational constraint counterpart, cyclic-CAla) (squares), onto the optimal 3D principal axes. The symbols indicate the projected conformations, and the ellipsoids engulf the volume occupied by the projected points. This projection shows that the conformational volume accessible to the cyclic analog is only a small subset of the conformational volume accessible to the linear peptide, (Adapted from Ref. 41.)...

Y Levy, CM Becker. Effect of conformational constraints on the topography of complex potential energy surfaces. Phys Rev Lett 81 1126-1129, 1998. 

An explanation for the stereoselectivity of the reaction involves optimal overlap of the 7t-orbital of the carbonyl with the developing electron rich p-orbital on C2 during the Sj,j2 displacement of the chloride by the alkoxide (24). Thus, orbital overlap imposes conformational constraints in the transition state that leads to nonbonding interactions disfavoring transition state 15P... 

C12-C13 would facilitate the ring closure, monocyclic diene 170 was chosen as the metathesis substrate. Indeed, exposure of 170 to catalyst A provided cycliza-tion product 171 in 94% yield within 6 h, without the aid of a cyclic conformational constraint. 

The raw materials from which di-D-fructose dianhydrides can be obtained in appreciable yield are readily available from comparatively inexpensive agricultural feedstocks. Thus, these compounds are attractive as chiral-starting materials for chemical synthesis. Their stability to acid and heat, and their relative rigidity, because of the conformational constraints covered here, are also features that might be exploited during syntheses.119 A series of variously substituted di-D-fructose dianhydrides has been prepared,119 starting from 6,6 -dideoxy-6,6 -di-halosucroses. The properties of these and other derivatives of di-D-fructose dianhydrides are summarized in Tables XIV-XX. Two of these derivatives, 48 and 56, exhibit thermotropic liquid-crystal properties.119... 

Finally, we should mention that the asymmetry of molecular shape, polyphilic effects and conformational constraints are the dominant factors in the stabilization of polar ordering in achiral mesogens. The examples presented above are, therefore, highly significant. They show that many liquid crystalline structures are intrinsically polar and may be effectively stabilized by suitable design of the mesogenic molecules. 

The strategy of introducing non-natural aminoacids into the oxytocin peptide skeleton in order to make antagonists has also been exploited by Havaas et al. [51], who replaced the proline at the 7-position with sarcosine and modified the tyrosine residue at the 2-position to introduce further conformational constraint. A representative example is shown, (13), with a... 

Cross-links, which impose strong conformational constraints on the intervening segment of the chain, generally are not classified as elements of secondary or tertiary structure. Disulfide cross-links in protein may certainly stabilize both secondary and tertiary structure, and such cross-links have the... 

DiMaio J, Nguyen TM-D, Lemieux C, Schiller PW. Synthesis and pharmacological characterization in vitro of cyclic enkephalin analogs effect of conformational constraints on opiate receptor selectivity. J Med Chem 1982 25 1432-1438. 

In the x-ray structure of rhodopsin, an amphipathic helix runs parallel to the membrane from the intracellular end of TM-VII beneath the seven-helical bundle to the other side of TM-I and TM-II. At this point, one or more Cys residues are often found and are known to be subject to a dynamic posttranslational modification with palmitic acid residues. Like the phosphorylation event, the palmitoylation process appears to be dynamically regulated by receptor occupancy and is also involved in the desensitization phenomenon. The two posttranslational modifications can influence each other. For example, the conformational constraint induced by palmitoylation may alter the accessibility of certain phosphorylation sites. Like the phosphorylation process, the functional consequences of palmitoylation also appear to vary from receptor to receptor. 

Further examples of cavitand-type structures include hw-cyclo-triveratrylene derivatives such as (257) (Gabard Collet, 1981 Canceill, Lacombe Collet, 1986) and the bowl-shaped hosts represented by (258) - the base of the bowl is formed by the four methyl groups. Once again, the shape of these molecules is maintained by conformational constraints. Cavitand (258) is able to accommodate simple solvent molecules such as dichloromethane and chloroform. Moreover, its cavity is large enough to form inclusion complexes with up to four molecules of water (Moran, Karbach Cram, 1982). 

The bias of a given diene for RCM depends on the ring size formed, on conformational constraints of the substrate, on the presence of functional groups, and on interactions with the specific catalyst used. 

Uversky, V. N., and Fink, A. L. (2004). Conformational constraints for amyloid fibrillation The importance of being unfolded. Biochim. Biophys. Acta Proteins Proteomics 1698, 131-153. 

Van Duin, A.C.T. and Collins, MJ. (1998). The effects of conformational constraints on aspartic acid racemization. Organic Geochemistry 29 1227-1232. 

For N-linked chains, it is pertinent to discuss the latter aspect, for which some constraints on degrees of freedom have been established. For O-linked chains, a picture in which the chains can be said to be in intimate contact with the protein, imposing conformational constraints and allowing for joint oligosaccharide-protein determinants, is emerging. 

The structure of this chapter is as follows Section 2.2 introduces the various types of conformational constraints used in NMR structure calculations. Section 2.3 is devoted to modern structure calculation algorithms. Section 2.4 gives an account of the general principles and the practice of automated NOESY assignment. 

For use in a structure calculation, geometric conformational constraints have to be derived from suitable conformation-dependent NMR parameters. These geometric constraints should, on the one hand, convey to the structure calculation as much as possible of the structural information inherent in the NMR data, and, on the other hand, be simple enough to be used efficiently by the structure calculation algorithms. NMR parameters with a clearly understood physical relation to a corresponding geometric parameter... 

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