Peptide bond stability Subject

Stability problems also manifest in vivo. Potential peptide and protein drags are subject to degradation by numerous enzymes or enzyme systems throughout the body. Degradation involves hydrolytic cleavage of peptide bonds by proteases (Figure 1.11) ... 

Cydo-fSarg) (70) was subjected to further invest ations and was proved to assume the same conformation in crystalline state as in solution, where the peptide bond had a cis-cis-trans-tramtrans-trans sequence. As stated earlier, in cyclic peptides made of N-unsubstituted amino acids, formation of the tum accompanied with intramolecular hydrogen bonds contributes to the stabilization of the ringstruc-... 

The greater stability of 120 relative to 123 induced us to center our efforts on luzopeptin E2. It seemed logical to examine first a macrolactonization strategy involving cyclodimerization of 125, because we estimated that the coupling of acid 124 with amine 49 would not be subject to the stereochemical difficulties alluded to in the introduction, and that no base treatment would be necessary subsequent to the union of 124 and 49 through peptide bond formation. Recall that peptides incorporating mhv are base-sensitive this property was likely to be carried over into 125. 

Hydrogen bonding is also believed to play a role in photodegradation [587]. The following mechanism has been proposed to explain the stability of peptide bonds subjected to light ... 

In order to facilitate the generation of peptide thioesters, several groupst have developed generalized versions of the thioester linker pioneered by Hojo and Aimoto.f A 3-sulfanylpropanoic acid residue is generated on an acid-labile linker such as Boc-Leu-PAM-resin or Boc-Leu-MBHA-resin. It is important to have a one-residue spacer between the MBHA linker and the thiol for optimal acid stability of the amide bond.f All twenty Boc-protected amino acids can be coupled to this thiol on the solid support to generate the thioester.Despite the potential reactivity of the thioester to the amino terminus, the formation of a dioxopiperazine is not generally observed when using in situ neutralization protocols. However, when the sequence was Leu-Tyr-Arg-Ala-Pro, 20% of a dipeptide deletion product, Leu-Tyr-Arg, was observed. It is likely that sequences such as C-terminal Pro-Gly would also be subject to this side reaction.t ... 

Substrate selection is thus subject to controls at (a) the recognition level, (b) formation of the adenylate, (c) stability of the adenylate, (d) transfer of the acyl residue to the cofactor (aminoacylation or acylation), (e) stability of this acyl intermediate, (f) proper functioning of the acyl intermediate in peptide (or ester) bond formation, and (g)... 

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