Peptides conformational equilibria

Figure 4.6. Modulation of peptide conformational equilibrium can be achieved through systematic modifications of peptide sequences that direct receptor interactions toward therapeutic response, and away from untoward effects. A systematic peptide modification may lead to reduced concentrations of peptide conformations susceptible to metabolizing enzymes such as peptidases.

Analogously, the fluorescence quantum yield of an extrinsic fluorescent probe contained in a peptide can be measured by comparison with an appropriate standard. If the fluorescent peptide exists in a conformational equilibrium, the fluorophore may be located in a number of different environments and may have a distinct quantum yield (ip,) in each environment. In this case the determined fluorescence quantum yield represents a population-weighted average of the individual [Pg.700]

Fig. 1. The conformational equilibrium in short peptidic structures lies towards the structureless form...

Let us now turn to the results obtained in the simulation of various typical secondary structures found in peptides and proteins, using equation (2). We shall focus on the importance of allowing flexibility of the molecular geometry and the necessity for accounting for dynamic effects, especially low frequency deformation modes, in order to describe conformational equilibrium in... 

An influence of A-glycosylation on peptide conformation has also been observed by Danishefsky et al. upon attachment of the non-natural trisaccharide Gal(/3 l-6)Gal(/3 l-6)GlcNAc /3-N-glycosidically to the Asn side chain of the model peptide H-Ala-Leu-Asn-Leu-Thr-OH [74]. Whereas the unglycosylated peptide failed to manifest any appreciable secondary structure, the glycopeptide was assumed to exist in an equilibrium between an ordered and a random state. When carried out at -12 °C using a 90 10 mixture of H20/acetone-[Pg.1779]

The minimum number of amino acids required to form a P-sheet is usually 6-7 and around 12-13 for an a-helix. For such small peptides it is possible to predict the specific secondary structure (a-helix, P-sheet, P-tum) as well as the orientation of side chains (Fig. 9.2.12), thereby allowing an efficient design. For shorter peptides the conformational equilibrium is displaced towards the unordered coil, and for large peptides predictions are still impossible. 

The thermodynamic data has been determined by Kimura et for the side-chain conformational equilibrium of aspartic acid residue in both model Asp peptides (di- to tetra-) and neuropeptide achatin-I (Gly-D-Phe-Ala-Asp) in aqueous solution by the use of vicinal HH couplings. 

Vicinal couplings between protons have been used not only to study peptide conformation, but also to study conformational equilibria within ring systems, such as found in proline. Jhh have shown that the proline ring exists in an exo-endo equilibrium, which varies with pH (Pogliani et a/., 1975 Jankowski et al, 1978). 

Conformational free energy simulations are being widely used in modeling of complex molecular systems [1]. Recent examples of applications include study of torsions in n-butane [2] and peptide sidechains [3, 4], as well as aggregation of methane [5] and a helix bundle protein in water [6]. Calculating free energy differences between molecular states is valuable because they are observable thermodynamic quantities, related to equilibrium constants and... 

The free energy differences obtained from our constrained simulations refer to strictly specified states, defined by single points in the 14-dimensional dihedral space. Standard concepts of a molecular conformation include some region, or volume in that space, explored by thermal fluctuations around a transient equilibrium structure. To obtain the free energy differences between conformers of the unconstrained peptide, a correction for the thermodynamic state is needed. The volume of explored conformational space may be estimated from the covariance matrix of the coordinates of interest, = ((Ci [13, lOj. For each of the four selected conform-... 

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