Peptides folded backbones

Finally, there is the case of the tetrapeptide LPro-LTyr-Llle-LLeu-OH, a fragment of neurotensin, which has a folded backbone but in which internal NH 0=C bonding does not occur (Cotrait et ai, 1979). The molecule has an approximate H shape in which the four side chains are extended in the legs of the H and the center bar consists of the peptide unit between L-tyrosine and L-isoleucine. 

Figure 25 Backbone thioester exchange for the quantification of peptide folding interactions.

Moreover, peptide amphiphiles have been revealed as promising candidates for MRI and biomaterial scaf-folds." " Gd " "-based MR contrast agents have been covalently attached to peptide amphiphile backbones, which noncovalently self-assemble into nanofibers. The position of the Gd " " complex on the backbone was investigated in order to optimize relaxivity. These supramolecular probes exhibited high relaxivity values (up to 21.5 mM s ) and significant MR contrast enhancement was observed in vitro in comparison to a Gd-DTPA standard. Gd +-modified peptide amphiphiles have potential application in nonin-vasive tracking of biomaterial implants in vivo. 

Fig. 5 Gallery of NH-)t interactions between an aromatic residne (Phe, Tyr or Tip) and a backbone amide NH bond, from gas phase IR/UV laser spectroscopy of a series of model capped peptides a folded backbone (y-tum), without and with a NH-ic interaction within the Phe residue [70], an extended backbone on Phe, with the interaction of Phe with NH of the next residue [84, 94]) and various aryl-rich dipeptides, leading to sandwich-Uke conformations of the NH embedded in the aryl environment and to significantly red shifted IR NH stretch signatures [112]. In the latter cases, the simultaneous presence of two it H-txaids raiginating from the same NH moiety (made possible through a direct interactiim between aromatic side chains) is indicated by the 3D-NCI plot of these interactions [193, 194]...

Scheme 17.28. Peptide folding can explain the role of the nonmobile proton in peptide backbone cleavage.

While the a-helix of L-a-peptides and the (M)-3i4 helix of the corresponding peptides have opposite polarity and helicity (see Section 2.2.3.1), the inserhon of two CH2 groups in the backbone of L-a-amino acids leave these two hehx parameters unchanged, both the a-helix and the 2.614-hehx of the resulting y" -peptides being right-handed and polarized from N to C terminus. In view of these similarities, the y-peptide hehcal fold might prove useful as a template to elaborate functional mimetics of bioachve a-polypeptides. 

Protein stability is just the difference in free energy between the correctly folded structure of a protein and the unfolded, denatured form. In the denatured form, the protein is unfolded, side chains and the peptide backbone are exposed to water, and the protein is conformationally mobile (moving around between a lot of different, random structures). The more stable the protein, the larger the free energy difference between the unfolded form and the native structure. 

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