Conformation of oligopeptides

A better understanding of the relation between physicochemical properties and conformation of oligopeptides has been possible by the application of the so-called host-guest technique in the liquid phase method of peptide synthesis. This technique was originally introduced to obtain detailed information regarding the thermo-... 

The computation of stable conformations of oligopeptides then involves three different problems First, the geometry (bond lengths and bond angles) of the chain must be known, and the functional form (and the values of the parameters) of U and V must be determined. Second, the sum U + V must be minimized to locate the various local minima. Third, the vibrational (conformational) entropy of each minimum within a reasonable range of the global one, that is, within about 1 kcal/mol, must be calculated to locate the global minimum of G. 

The ESMC method in the form of the multicanonical MC has been used to simulate conformations of oligopeptides by Hansmann and Okamoto [42,44,45]. These studies were aimed at determining the canonical properties of the molecules and searching for the low-energy conformations. Therefore, only approximate multicanonical functions, for example, with no convergence check on these functions, were used in the conformational sampling. It was reported that, for the small polypeptides studied, about... 

The chain length dependence of the conformation of oligopeptides of L-lysine in aqueous solutions was investigated, and it was found that at pH 4.3 not even a chain of 22 residues showed an ordered structure (Yaron et al, 1971). At pH 11.9 the onset of helicity was observed at 12 residues. 

CD spectroscopy also proved to be useful for systematically studying the influence of the concentration on the conformation of oligopeptides Conformational transitions of the type P-structure - random coil can be compelled by diluting solutions of peptides with a potential to adopt a pleated sheet. This procedure permits the distinction between inter- and intramolecular p-structures ( cross-P-structures )- Cross-P-structures are characterized by a backfolding of the peptide chain the intramolecular aggregation is insensitive to disruption by dilution. 

Takeldyo, T., hnai, T, Kato, M, Taniguchi, Y. (2006a) Understanding High Pressure Stability of Helical Conformation of Oligopeptides and Helix Bundle Protein -High Pressure FT-IR and RISM Theoretical Studies-, Biochim. Biophys. Acta Vol. 1764 355-363. 

Today in empirical energy computations on conformation of oligopeptides, free energy terms introduced to account for hydration are included... 

E Benedetti, G Morelh, G Nemethy, HA Scheraga. Statistical and energetic analysis of side-chain conformations m oligopeptides. Int J Peptide Pi otem Res 22 1-15, 1983. 

The third current approach is synthesis of peptide chains as models for the helical peptaibol (Section 8.2) and gramicidin (Section 8.3) ion channels. Considerable work has been carried out in the former area, involving synthesis of Aib-containing small peptides, in order to obtain conformational data applicable to the more complex oligopeptide antibiotics. By working with such fragments it has been possible to obtain valuable X-ray crystal structure information on the helical conformation of ala-methin 246), emerimicin 247), suzukacillin 248), and other members of the peptaibol series. 

A protein is a linear sequence of amino acids linked together by peptide bonds. The peptide bond is a covalent bond between the oi-amino group of one amino acid and the a-carboxyl group of another. The peptide bond has partial double bond character and is nearly always in the trans configuration. The backbone conformation of a polypeptide is specified by the rotation angles about the Ca-N bond phi, (j>) and Ca-C bond psi, amino acid residues. The sterically allowed values of 0 and yr are visualized in a Ramachandran plot. When two amino acids are joined by a peptide bond they form a dipeptide. Addition of further amino acids results in long chains called oligopeptides and polypeptides. 

Fig. 5.5 A model of conformational autocatalysis for the oligopeptide of Fig.5.4. The lowest-energy a-helical form (two-helix bundle, left-hand side) interacts with the frozen metastable (3 form (four-member (3 barrel, center). After a long Monte Carlo run (symbolized by an arrow), which consists of a million of intermediate conformations of various type, both molecules form a strong complex of two (3 type metastable forms right). During this run the a conformation unfolds and then refolds to the (3 conformation. Thus, the (3 metastable form plays a role of a catalyst in the transformation of the a native structure into the (3 form (autocatalysis)...

The calculations represented in Figure 8 illustrate the simple fact that atoms occupy space that is, the hard-sphere potential already provides a considerable amount of restriction on the allowed conformations of terminally blocked amino acid residues and hence of oligopeptides built up from such residues. This fact will remain true, to a first approximation, even when more realistic energy functions are introduced. 

The average conformation of the oligopeptide chain is then taken as the combination of the average values of 4> and i / for all individual residues. 

C. S. C. Wu, A. Hachimori, J. T. Yang, Lipid-induced ordered conformation of some peptide hormones and bioactive oligopeptides predominance of the helix over the beta-form. Biochemistry 1982, 21, 4556-4562. 

D. Seebach, J. V. Schreiber, S. Abele, X. Daura, W. F. van Gunsteren, Structure and Conformation of P-Oligopeptide Derivatives with Simple Proteinogenic Side Chains Circular Di-chroism and Molecular Dynamics Investigations , Helv. Chim. Acta (2000, 83,34 - 57. 

Poly(amino acids) are attractive enzyme models because of their structural similarity. In fact, characteristic pH dependences of the cataljrtic rate were found and this was considered to reflect the conformational peculiarity of poly(amino acids). Unfortur nately, rate enhancements are only moderate and characterization of the catal3rtic site is difficult. Interesting results were obtained in the catalysis of oligopeptides, which supposedly mimic the active site of some hydrolytic enzymes. The stereoselectivity seems to be realized with oligopeptides more easily than with vinyl polymer catalysts. 

Imawaka N, Tanaka M, Suemune H. The first fully planar Cs-conformation of homo-oligopeptides prepared from a chiral a-ethylated a,a-disubstituted amino acid (S)-butylethylglycine [= (2S)-2-amino-ethylhexanoic acid]. Helv. Chim. Acta 2000 83 2823-2835. 

Though this peptide has considerably increased conformational flexibility over the cyclic peptide tentoxin, it contains two backbone and side chain modifications which confer increased conformational rigidity to the molecule when compared with backbone non-mod1fied oligopeptides. It is helpful to recall that the conformation of a peptide is determined by its overall three-dimensional structure (14). If the bond angles and bond... 

Figure 2.7. Aggregated conformations of an amphiphilic oligopeptide, (a) Aggregated antiparallel (i-sheets at pH 4. (b) a-helices aggregating at pH 7.

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