Trans peptide bond

Wilkes BC, Nguyen TM-D, Weltrowska G, Carpenter KA, Lemieux C, Chung NN, Schiller PW. The receptor-bound conformation of H-Tyr-Tic-(Phe-Phe)-OH related -opioid antagonists contains all trans peptide bonds. J Peptide Res 1998 51 386-394. 

Fig. 1. Conformational energy diagram for the alanine dipeptide (adapted from Ramachandran et al., 1963). Energy contours are drawn at intervals of 1 kcal mol-1. The potential energy minima for p, ofR, and aL are labeled. The dependence of the sequential d (i, i + 1) distance (in A) on the 0 and 0 dihedral angles (Billeter etal., 1982) is shown as a set of contours labeled according to interproton distance at the right of the figure. The da (i, i + 1) distance depends only on 0 for trans peptide bonds (Wright et al., 1988) and is represented as a series of contours parallel to the 0 axis. Reproduced from Dyson and Wright (1991). Ann. Rev. Biophys. Chem. 20, 519-538, with permission from Annual Reviews.

IR spectroscopy permits reliable discrimination between cis and trans-secondary amide bonds and the presence of 1550 cm bands is indicative of trans-peptide bonds (Table 2). 

Figure 1 (Left) Model of the receptor-bound conformation of TIP containing all-trans peptide bonds (heavy lines) in spatial overlap with naltrindole (light lines). (Right) Model of the receptor bound conformation of H-Tyr-Tic-NH2 containing a cis peptide bond (heavy lines) in spatial overlap with naltrindole (light lines). In both cases the N-terminal amino group and the Tyr1 and Tic2 aromatic rings of the peptide are superimposed on the corresponding pharmacophoric moieties in the alkaloid structure.

In addition to the order-disorder transition, observed for a helices, helical structures can also be induced to undergo transitions from one ordered form to another. For example, a crystalline form of poly[p-(p-chlorobenzyl)-L-aspartate] can be made to undergo a phase transition from an a-helical to an co-helical form by heating rotational entropy is computed to play a role in this process.68 Another order-order transition is the solvent-induced interconversion between polyproline 1 (with cis peptide bonds) and polyproline 11 (with trans peptide bonds), a process that has also been subjected to conformational energy calculations.85 The transition has been accounted for in terms of differences in the binding of solvent components to the peptide 0=0 groups. 

Cis as well as trans peptide bonds occur in cyclic peptides containii imino add residues... 

Fig. 5. Gs and trans peptide bonds as shown with N-acetyFN-methylalanine dimethylamide...

Cydo-(Pro-Sai>-Gly)2 CDQ3 CD3OD DMSO 1 C2-symmetric conformation two -tums with two Gly-NH intra H-bond all trans peptide bonds 92% in CDQs, 88% in CD3OD, 76% in DMSO 1 asymmetric conformation one CIS and one trots Pro-Sai peptide bonds one intra and one inter Qy-NH H-boid... 

Figure 22-4. The geometry of the peptide backbone, with the trans peptide bond, showing all the atoms between two C atoms of adjacent residues. (Reprinted from reference 31, with permission.)...

Parameters Characterizing the Theoretically Computed Minimum-Energy Conformations of cyclo(L-Ala—Gly-Aca) with Trans Peptide Bonds... 

NMR and CD spectroscopy revealed the existence of several conformations of the cyclopeptide and its complexes27,62 In non-polar solvents, a C3 symmetric conformation with trans peptide bonds and three 3 - 1 type hydrogen bonds exists. From this conformation, the complex is formed by rotation of the peptide bond units between Pro and Gly residues (Fig. 46). The complex conformation retains C3 symmetry and all -trans peptide bonds, but it is devoid of intramolecular hydrogen bonds. In polar solvents, cyclo-(L-Pro-Gly)3 forms an unsymmetric conformation with one cis Gly-Pro peptide bond. 

Backbone dynamic experiments indicated a significant mobility for the trans peptide bond whereas the cis form is conformationally more restricted [148]. Each of the conformers binds ligands with different chemical properties. The trans con-former preferentially binds phosphotyrosine-containing peptides. When resuming the cis conformation the SH2 domain builds a specific intermolecular complex with the Src homology 3 (SH3) domain of ITK. This serves to restrict access to the catalytic domain. Both domains, the SH2 and the SH3, influence the conformational properties of the neighboring kinase domain and render the catalytic domain unable to carry out its physiological function [149]. This shows that pep-... 

The relevance of catalyzed and spontaneous peptide bond CTI to the biological function of peptides and proteins has inspired considerable effort in research. Thus, distinct pathways have been identified that allow peptide bond isomers to affect physiological signaling differently. To fully understand isomer specificity of bioreactions at the molecular level, it is essential to characterize the structural and electronic differences between cis and trans peptide bond isomers. Most importantly, both isomers cannot sample the same conformational space around proline [30,171], thus presenting an isomer-specific topography to interacting molecules. 

JTo facilitate reading I use the terms cis and trans proline for proline residues preceded by a cis or a trans peptide bond in the folded protein nativelike and incorrect, nonnative denote whether or not a particular prolyl peptide bond in an unfolded state shows the same conformation as in the native state. Further, I use the expression isomerization of Xaa for the isomerization of the peptide bond preceding Xaa. Peptide bonds preceding proline are referred to as prolyl bonds, and those preceding residues other than proline are termed as nonprolyl bonds. The folding reactions that involve Xaa—Pro isomerizations as rate-limiting steps are called proline-limited reactions. 

A cis-trans isomerase and a disulfide isomerase also participate in folding. The cis-trans isomerase converts a trans peptide bond preceding a proline into the cis conformation, which is well suited for making hairpin turns. The disulfide isomerase breaks and reforms disulfide bonds between the -SH groups of two cysteine residues in transient structures formed during the folding process. After the protein has folded, cysteine-SH groups in close contact in the tertiary structure can react to form the final disulfide bonds. 

---