Peptides thermodynamic stability

It is well known that native collagen containes tripeptide sequences, which alone are not capable of building up a triple helix (e.g. Gly-Pro-Leu, Gly-Pro-Ser) when they exist as homopolypeptides. The synthesis of threefold covalently bridged peptide chains opens up the possibility of investigating the folding properties of such weak helix formers, because the bridging reduces the entropy loss during triple-helix formation and thereby increases the thermodynamic stability of the tertiary structure. Therefore, we have... 

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). 

As a result of the branched chain architecture, TASP molecules exhibit some unique conformational properties)5 12-14 47 75 76 148 For example, the folding to a compact state proceeds via two distinct steps the onset of secondary structure in the attached peptide blocks followed by their template-directed self-assembly to a three-dimensional packing topology. Due to its characteristic branched chain connectivity, the conformational space accessible in the unfolded state is considerably reduced compared to a linear chain of similar size (excluded volume effect), resulting in a smaller chain entropy. Thus, folded TASP molecules are expected to show higher thermodynamic stability compared to unbranched polypeptides of comparable size. 

Powell MF, Fleitman J, Sanders LM, Si VC. Peptide liquid crystals inverse correlation of kinetic formation and thermodynamic stability in aqueous solution. Pharm Res 1994 11 1352-1354. 

Kremer, C., Torres, J., Dominguezb, S., and Mederos, A. (2005) Structure and thermodynamic stability of lanthanide complexes with amino acids and peptides. Coordination Chemistry Reviews, 249, 567-590. 

Despite this low thermodynamic stability the permanent existence of a single secondary amide peptide bond in cis conformation per 1000 amino acid residues is the minimal population that has to be considered for unfolded polypeptide chains. This cis peptide bond fluctuates across the polypeptide chain in relation to the sequence-specific propensity of a secondary amide peptide bond to adopt the cis conformation. As could be found in folded proteins, nonprolyl cis peptides are frequently located in the fS-region of a q>/y/ plot [22]. It was hypothesized that cis peptide bonds represent high-energy structures able to store potential energy for increasing chemical reactivity [23]. Interconversion rates for the reversible CTI of secondary amide peptide bonds typically lead to half times of about 1 s for dipeptides, which decreases about 4-fold when the peptide bond is positioned in the middle of a longer peptide chain. 

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