Peptides self-association

Figure 16.10 Oligomerization states of TFI2 (left) and TF2 (right) in micelles. Without the aid of hydrogen bonding, only fluorinated TF2 peptides self-associate into dimers, while TH2 remains monomeric.

Influence of Peptide Self-Association Affinity on Cd(II) Binding. 330... 

Insulin is composed of two peptide chains covalently linked by disulfide bonds (Figures 5.17 and 6.35). This monomer of insulin is the active form that binds to receptors in target cells. However, in solution, insulin spontaneously forms dimers, which themselves aggregate to form hexamers. The surface of the insulin molecule that self-associates to form hexamers is also the surface that binds to insulin receptors in target cells. Thus, hexamers of insulin are inactive. 

Coacervation occurs in tropoelastin solutions and is a precursor event in the assembly of elastin nanofibrils [42]. This phenomenon is thought to be mainly due to the interaction between hydro-phobic domains of tropoelastin. In scanning electron microscopy (SEM) picmres, nanofibril stmc-tures are visible in coacervate solutions of elastin-based peptides [37,43]. Indeed, Wright et al. [44] describe the self-association characteristics of multidomain proteins containing near-identical peptide repeat motifs. They suggest that this form of self-assembly occurs via specific intermolecular association, based on the repetition of identical or near-identical amino acid sequences. This specificity is consistent with the principle that ordered molecular assembhes are usually more stable than disordered ones, and with the idea that native-like interactions may be generally more favorable than nonnative ones in protein aggregates. 

Raguse, T. L., Lai, J. R., LePlae, P. R., and Gellman, S. H. Toward beta-peptide tertiary stmcture Self-association of an... 

In the search for fibril formation inhibitors, the self-association to form amyloid fibrils of the A(3 peptides containing 40 and 42 amino acids can be treated as a coupled protein folding and polymerization process passing through multiple intermediate peptide species. The in vitro challenge is (1) to identify the various conformational forms and... 

Terzi, E., Holzemann, G., and Seelig, J. (1995). Self-association of beta-amyloid peptide (1-40) in solution and binding to lipid membranes./. Mol. Biol. 252, 633-642. Terzi, E., Holzemann, G., and Seelig, J. (1997). Interaction of Alzheimer beta-amyloid peptide (1-40) with lipid membranes. Biochemistry 36, 14845—14852. 

One inherent property of peptides that interact with membranes is that self-association or even aggregation will interfere with solubilization by organic solvents or micelles. The preparation, purification and sample preparation of extremely hydrophobic (often transmembrane) peptides is nontrivial and has been addressed by only a few papers [74—79]. 

CaM), of fatty acid carboxylate to intestinal fatty acid binding protein (IFABP), and of peptides (e.g, melittin) to Ca +-saturated calmodulin (holo CaM)]. We also extended PLIMSTEX to protein-protein interactions involving self associations of various insulins [33]. These are widely studied systems, and their individual K values range from to 10 M h... 

Kar K, Amin P, Bryan MA, Persikov AV, Mohs A, Wang Y-H, Brodsky B. Self-association of collagen triple helix peptides into higher order structures. J Biol Chem 2006 281 33283-33290. 

Fig. 17. Fluorous patches direct the pairing of protein segments in lipid micelles. The hydrophobic peptides partition into lipid micelles, forming a-helices. Then, the superhydrophobic hexafluoroleucine residues seek each other, causing self-association into dimers and higher order aggregates. Fluorine is light, while the backbone of the a-helices is dark. From Ref. [81], with permission.

Fluorescence quantum yield and emission maximum determinations as a function of peptide concentration may also permit the detection of peptide self-aggregation at concentrations below 10-4 M, because the peptide fluorophore is likely to be located in a different environment in the peptide aggregate. For example, the concentration-dependent changes in the tryptophan fluorescence emission maximum of mellitin were monitored to determine the equilibrium dissociation constant and thermodynamic parameters of the monomer-tetramer self-association reaction of this peptide. 25 Similarly, measurement of the changes in the tryptophan fluorescence intensity of gramicidin A as a function of its concentration permitted the determination of an average monomer-dimer equilibrium con-stant. 26 ... 

From the concentration dependence of the polyphenol chemical shifts as a function of the polyphenol concentration in the absence and presence of peptide, it is clear that polyphenol self-association is only weakly affected by the peptide. Thus, peptide-polyphenol binding probably involves noncovalent polyphenol oligomers that are more effective than the corresponding monomers at developing interactions with a second peptide molecule to trigger precipitation. 

Thomas, R. M., Wendt, H., Zampieri, A., and Bosshard, H. R. (1995). Alpha-helical coiled coils simple models for self-associating peptide and protein systems. Prog. Coll. Polym. ScL, 99, 24-30. 

In biological recognition phenomena, protein-protein interactions are of primary importance. In an attempt to mimic these processes, LaBrenz and Kelly [51] synthesized the peptidic host 64. In this receptor, the dibenzofuran template separates the two peptide units by roughly 10 A and allows for the complexation of a guest peptide (65), as depicted in Fig. 21. The complex first forms a three-stranded, antiparallel /J-sheet that is stabilized by hydrogen bonds, electrostatic interactions, and aromatic-aromatic interactions between the dibenzofuran and the benzamide moieties. This complex can further self associate to form more complex structures. This example shows that structurally defined peptide nanostructures can interfere with biological recognition processes and potentially have therapeutic applications. 

Due to the preference for a cis-amide bond[93] with the preceding residue of C2-substituted pseudoprolines, their incorporation results in a kink conformation of the peptide backbone, thus preventing peptide aggregation, self-association, or (3-structure formation. 

Several laboratories have described systems by which synthetic linear peptide chains self-assemble into desirable secondary and tertiary structures. One self-assembly approach has been the creation of a peptide-amphiphile, whereby a peptide head group has the propensity to form a distinct structural element, while a lipophilic tail serves to align the peptide strands and induce secondary and tertiary structure formation, as well as providing a hydrophobic surface for self-association and/or interaction with other surfaces. The preparation of a dialkyl ester tail first involves the acid-catalyzed condensation of H-Glu-OH with the appropriate fatty acid alcohol to form the dialkyl ester of H-Glu-OH a typical example is shown in Scheme 7. The assembly of peptide-amphiphiles with mono- and dialkyl ester tails is shown in Scheme 8. A series of studies have demonstrated that triple-helical and a-helical protein-like molecular architecture is stabilized in the peptide-amphiphile 44,63-65 ... 

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