Backbone conformation, influence

The solution conformation of plastocyanin from French bean, spinach, and S. obliquus has now been determined from distance and dihedral angle constraints derived by NMR spectroscopy [37,40]. These two-dimensional NMR studies have indicated a well defined backbone conformation, which is very similar to that of poplar PCu in the crystalline state. However, in the case of S. obliquus there are deletions at positions S7 and 58 which influence the shape in the acidic region and in particular close to residues 59-61. The gap which is created is in effect repaired with consequent tightening of the loop 57-62 as indicated in Fig. 5. One of the pronounced bulges at the remote site of poplar and presumably other higher plant plastocyanins is not therefore present in S. obliquus (or plastocyanin from other green algae) [31, 32], as well as parsley... 

Morphology based on chemical environment can be probed using F NMR spectroscopy because the chemical shifts of F atoms in the side chains are considerably separated from those in the backbone. Conformational dynamics as affected by domain-selective solvent incorporation are reflected in the widths of static F peaks. These conformational motions, in turn, can influence the migration of solvent penetrants. 

Furthermore, in flexible linear peptides the chemical shifts are typical of random structures similar to nonfolded proteins. Deviation from these random shifts sometimes identifies specific conformational preferences. NH-proton chemical shifts depend strongly on external influences (solvent, temperature, concentration, specific sequence). Random coil shifts for these protons correlate less well than chemical shifts of the a-protons or a-carbonsJ19-261 Not only are the shift differences of different heterotopic protons similar, but also those of diastereotopic P-protons. A preferred side-chain conformation is normally only found when there is also a preferred backbone conformation. 

However, it was immediately recognized by peptide chemists that, even in the cases where a direct (backbone)peptide -protein(backbone) interaction is not operative, the backbone conformation may dramatically influence the biological response. It is evident that the introduction of new, promising peptidomimetics is based primarily on the combined knowledge of the complementary conformational, topochemical, and electronic properties of the native peptide and of its address (in other words, of the receptor or the active site of the enzyme with which it interacts). Then, the design of peptidomimetics as potential bioactive compounds must take into particular account two structural factors (i) a favorable fit (tertiary structure) with respect to the corresponding complementary spatial situation at the active site (ii) the placement of structural elements (e.g., functional groups, polar and... 

The conformational influence of Saa2, Saa3, and Saa4 on the peptide backbone of three cyclic peptides 27-29 (Figure 1) has been investigated in more detail by NMR spectroscopy, distance geometry (DG), and subsequent molecular dynamic (MD) calculations.1451... 

Considerations by V. Shibaev and N. Plate (see this issue) led to a similar conclusion. Investigations on comb like polymers26), where each monomer unit of the macromolecule carried a non-branched alkyl chain of m methylene groups, have shown that for m > 8 side chain crystallization takes place independently to the main chain conformation. Consequently, if mesogenic molecules are linked to the side chains, they should occupy a l.c. order without influence of the backbone conformation. Following these considerations, alkyl chain lengths m > 8 are necessary for the formation of the l.c. order. As shown later, however, nearly only smectic polymers are possible under these conditions (see Chap. 2.3.3.). 

Since the electronic absorption spectra of polvsilanes and polygermanes also depend strongly on conformation (3), these materials provide a unique opportunity to study the effect of backbone conformation on the NLO properties, particularly since varying alkyl substituents can dramatically influence the backbone structure through intermolecular interactions (e.g., side chain crystallization) while causing... 

VII. Influence of Glycosylation on Proteoglycan Core-Peptide Backbone Conformation. .. 213... 

In conclusion it has turned out to be difficult to polymerize all but the first generation dendritic macromonomer. Higher generation dendrimers need to be attached through a long series of bonds to the polymer backbone. This in turn prevents any strong conformational influence on the backbone and no interesting new properties have been detected so far. 

The introduction of conformational constraints should influence the backbone conformation without compromising any crucial side chain interaction with the receptor. 

A computational study of phosphazene oligomers has shown a profound influence of intramolecular interactions on the backbone conformation. A NP bonding model in terms of an ionic cr-bond and a n-bond induced by negative hyperconjugation has been proposed.Molecular dynamics simulations have been carried out for and [NP(OC6H4Me-4)2]n Calculations for... 

Complementary to the analysis of conformation-dependent chemical shifts, two-dimensional experiments that correlate anisotropic interactions may be used to study backbone conformation by MAS NMR. This is possible in particular for dipolar interactions, whose orientations are along the intemuclear vector, and for the carbonyl CSAs, which generally adopt a particular orientation with respect to the peptide plane (Fig. 3a). Under MAS, these interactions may be recoupled during the evolution and/or detection period of a two-dimensional correlation experiment, as discussed earlier. The resulting spectrum will contain cross peaks whose pattern is characteristic of the relative orientation of the two interactions being correlated. An alternative approach is to excite a state of 2QC between two neighbouring nuclei, which then evolves under the influence of two anisotropic interactions. 

Levitt took an opposite approach in calculating residue-residue interaction energies and based his calculations on theoretical considerations rather than empirical distributions. He assumed that the interaction between side chains would be the average of the calculated interaction over all possible spatial orientations of the two residues. This assumption is hampered by the fact that side chain structures favor certain interaction geometries in folded proteins." Backbone conformations also influence side chain dihedral angles. ... 

While this monocyclic reverse-turn template clearly mimics the backbone conformation and side-chain presentations of p- and "y-tums quite well, one concern with such a large macrocycle is that the relatively flexible peptide backbone conformations are strongly influenced by the side-chain-side-chain interactions, as investigated by NMR solution structure (Fig. 29.11). ° We therefore needed a new type of turn mimetic bearing a constrained and rigid skeleton which could potentially enhance binding and/or improve bioavailability. Based on the conformational analyses of several heterobicyclic systems, we envisioned... 

Secondary structures are regular elements such as a-helices and p-pleated sheets, which are formed between relatively small parts of the protein sequence. These structural domains are determined by the conformation of the peptide backbone, the influence of side-chains is not taken into account for secondary structures. 

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