Peptides kinetic stability

Coordinated a-amino amides can be formed by the nucleophilic addition of amines to coordinated a-amino esters (see Chapter 7.4). This reaction forms the basis of attempts to use suitable metal coordination to promote peptide synthesis. Again, studies have been carried out using coordination of several metals and an interesting early example is amide formation on an amino acid imine complex of magnesium (equation 75).355 However, cobalt(III) complexes, because of their high kinetic stability, have received most serious investigation. These studies have been closely associated with those previously described for the hydrolysis of esters, amides and peptides. Whereas hydrolysis is observed when reactions are carried out in water, reactions in dimethyl-formamide or dimethyl sulfoxide result in peptide bond formation. These comparative results are illustrated in Scheme 91.356-358 The key intermediate (126) has also been reacted with dipeptide... 

From the point of view of prebiotic chemistry, it can be concluded from the thermodynamic and kinetic stability of amides that the formation of prebiotic peptides has very probably required catalysts and/or dehydrating or activating agents. But their spontaneous formation could not be com-... 

The chemical bonding in peptide bonds is responsible for their kinetic stability. Specifically, the resonance structure that accounts for the planarity of a peptide bond (Section 3.2.2) also makes such bonds resistant to hydrolysis. This resonance structure endows the peptide bond with partial double-bond character ... 

The groove can be filled by a peptide from 8 to 10 residues long in an extended conformation. As we shall see (Section 33.5.6). MHC proteins are remarkably diverse in the human population each person expresses as many as six distinct class I MHC proteins and many different forms are present in different people. The first structure determined, HLA-A2, binds peptides that almost always have leucine in the second position and valine in the last position (Figure 33.25). Side chains from the MHC molecule interact with the amino and carboxyl termini and with the side chains in these two key positions. These residues are often referred to as the anchor residues. The other residues are highly variable. Thus, many millions of different peptides can be presented by this particular class I MHC protein the identities of only two of the nine residues are crucial for binding. Each class of MHC molecules requires a unique set of anchor residues. Thus, a tremendous range of peptides can be presented by these molecules. Note that one face of the bound peptide is exposed to solution where it can be examined by other molecules, particularly T-cell receptors. An additional remarkable feature of MHC-peptide complexes is their kinetic stability once bound, a peptide is not released, even over a period of days. 

As already mentioned, these acyclic BFCs have favorable labeling kinetics for most metals, but they often lack kinetic stability. In fact, DTPA coupled via one of the five carboxylic acid functions is not suitable for any other radionuclide than In because of its in vivo instability (Harrison et al. 1991). Attempts to use DTPA-peptide conjugates labeled with for therapy... 

The peptide and thio-peptide bonds have some specific properties like coplanarity, substantial rotational barrier and kinetic stability towards nucleophilic attack or hydrolysis. All these properties are easily rationalized by the... 

This stability is confined to the FAD-peptide Tyr-Thr-Cys(FAD)-Tyr and it has been suggested (89), that either adenylate or tyrosine residues, or both, bring about stabilization through complexation in a way which has not yet been defined in chemical terms. In the opinion of the present author, the thermodynamic stabilization due to formation of molecular complexes should be minimal, while kinetic stabilization seems not to apply. Thus, formation of a macrocyclic thioacetal, possibly with the phenolic hydroxyl function of tyrosine (or with the threonine hydroxyl group) would better explain the unusual stability. 

One may conclude that the rate-determining step of the renaturation is at least partly influenced by the cis-trans isomerization of the peptide bond the secondary nitrogen atom of which arises from proline. Otherwise, only the entropy-controlled slow nuclea-tion should be observed kinetically. The covalent bridging through Lys-Lys, therefore, gives rise not only to thermodynamic stabilization of the triple helix but also to kinetic properties which have hitherto been observed in the case of type III procollagen146) and its aminoterminal fragment Col 1-3144). 

Fowles LF, Beck E, Worrall S, et al.The formation and stability of imidazolidinone adducts from acetaldehyde and model peptides. A kinetic study with implications for protein modification in alcohol abuse. Biochem. Pharmacol. 1996 51 1259-1267. 

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