Peptide chain, conformation

Connection of peptide-chain conformation with aA peak near 2300 A... 

Globular protein (M.W. -66500 Da) isoelectric point - 5.1 characteristic secondary structure, with a specific content of a-helix, -sheet and disordered peptide chain conformations presence of disulphide bonds and one free sulphydryl group... 

G. Montagnoli, O. Pieroni, and S. Suzuki, Control of peptide chain conformation by photo-isomerising chromophores Enzymes and model compounds, Polym. Photochem. 7, 279-294 (1983). 

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. 

In order to examine whether this sequence gave a fold similar to the template, the corresponding peptide was synthesized and its structure experimentally determined by NMR methods. The result is shown in Figure 17.15 and compared to the design target whose main chain conformation is identical to that of the Zif 268 template. The folds are remarkably similar even though there are some differences in the loop region between the two p strands. The core of the molecule, which comprises seven hydrophobic side chains, is well-ordered whereas the termini are disordered. The root mean square deviation of the main chain atoms are 2.0 A for residues 3 to 26 and 1.0 A for residues 8 to 26. 

Figure 17.15 Schematic diagrams of the main-chain conformations of the second zinc finger domain of Zif 268 (red) and the designed peptide FSD-1 (blue). The zinc finger domain is stabilized by a zinc atom whereas FSD-1 is stabilized by hydrophobic interactions between the p strands and the a helix. (Adapted from B.I. Dahiyat and S.L. Mayo, Science 278 82-87, 1997.)...

Pleated p sheet (Section 27.19) Type of protein secondary structure characterized by hydrogen bonds between NH and C=0 groups of adjacent parallel peptide chains. The individual chains are in an extended zigzag conformation. 

Substitution of a dipeptide unit by a cychc dipeptide derivative within a peptide chain can induce certain conformational restraints that may alter the biological response via changing receptor selectivity. A facile procedure for synthesis of pyrazinone ring-containing opioid mimetics [21] has been elaborated, based on the cycHzation of readily available dipep-tidyl chloromethyl ketones [22] (Scheme 6). This method affords 2(IH)-pyrazinone derivatives containing substituents with desired functional groups at positions 3 and 6 in high yield. 

Before analyzing in detail the conformational behaviour of y9-peptides, it is instructive to look back into the origins and the context of this discovery. The possi-bihty that a peptide chain consisting exclusively of y9-amino acid residues may adopt a defined secondary structure was raised in a long series of studies which began some 40 years ago, on y9-amino acid homopolymers (nylon-3 type polymers), such as poly(/9-alanine) 3 [14, 15], poly(y9-aminobutanoic acid) 4 [16-18], poly(a-dialkyl-/9-aminopropanoic acid) 5 ]19], poly(y9-L-aspartic acid) 6 ]20, 21], and poly-(a-alkyl-/9-L-aspartate) 7 [22-36] (Fig. 2.1). 

Coupling constants are routinely used to determine the side-chain conformation of amino acids in peptides and proteins. Whereas proteins nowadays are almost exclusively studied as C- and N-labeled isotopomers, peptides usually have these isotopes in natural abundance, i.e. the magnetically active heteronuclei are highly diluted. Most amino acids contain a methylene group at the ji-position for which the X angle is determined by the conformation of the Ca—Cp bond. Two vicinal Jhh coupling constants can be measured Ha to and H to Usually... 

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. 

Other than an effect on backbone solvation, side chains could potentially modulate PPII helix-forming propensities in a number of ways. These include contributions due to side chain conformational entropy and, as discussed previously, side chain-to-backbone hydrogen bonds. Given the extended nature of the PPII conformation, one might expect the side chains to possess significant conformational entropy compared to more compact conformations. The side chain conformational entropy, Y.S ppn (T = 298°K), available to each of the residues simulated in the Ac-Ala-Xaa-Ala-NMe peptides above was estimated using methods outlined in Creamer (2000). In essence, conformational entropy Scan be derived from the distribution of side chain conformations using Boltzmann s equation... 

These results strongly suggest that unstructured peptides have definite backbone conformations and that the concept of a denatured protein as a structureless random chain breaks down when backbone conformations of individual residues are described, although the random chain concept may still be useful when describing the overall chain conformation. 

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