Peptide amphiphilic structure

Fig. 7 Peptide Amphiphile Structure and Self-Assembly. From Intermolecular Forces in the Self-Assembly of Peptide Amphiphile Nanofibers by J.C. Stendahl, M.S. Rao, M.O Guler, and S.I. Stupp. Advanced Functional Materials, 6(4), p. 499. Copyright 2006 by Wiley-VCH Verlag GmbH Co. KGaA.

Fig. 2 The structure of (a) 20 natural L amino acids and (b) aromatic residues that gives rise to (c) aromatic peptide amphiphiles, which form supramolecular polymers through hydrogen bonding and 71-stacking interactions...

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 ... 

Early studies on amino acid/peptide derived amphiphiles revealed that their ability to assemble into various architectures was controlled by surprisingly small structural differences. The hydrophobic residues in the peptide amphiphiles have shown to shield themselves from water and to self-assemble in a manner similar to the protein folding. The similarity of their self-assembling properties to those of proteins, initiated numerous studies for the determination of the relationship between the structure of an individual amino acid or a specific peptide sequence and the resulting architecture. 

All the characteristics expressed in the biological lipids and phospholipids are also expressed in peptide amphiphiles. A variety of alkyl and dialkyl oligoglutamates will be initially discussed as representative of such molecules, which helped in the determination of the structure/assembly relationship (Figure 7.9). The latest advances that demonstrate how using this knowledge, peptide-derived materials were tailored for the construction of functional nanostructures amphiphiles will also be discussed. 

FIGURE 7.15. Molecular structure of a peptide amphiphile that self-assembles into a cylindrical aggregate. The five key structural elements of die peptide are highlighted. The cylindrical aggregate assembles into fibers that template the mineralization of die hydroxapatite crystal. The c axis of the crystal is aligned with the long axis of... 

The utilization of peptide self-assembly additionally allows control of structural parameters and the rational control of functionalities, which are displayed at the nanofiber surface. This makes the presentation of biological signals and thus the introduction of bioactivity feasible. Stupp and coworkers investigated the self-assembly of peptide-amphiphiles (Fig. 4) [87, 115], The resulting worm-like, cylindrical nanostructures consist of a hydrophobic core that is formed by the alkyl... 

Stupp, S.I., and Guler, M.O. Branched Peptide Amphiphiles, Related Epitope Compounds and Self Assembled Structures Thereof, 2004-US40546 2005056576 (2005). 

Artificial catalysts have also been incorporated into amphiphilic structures (Guler and Stupp, 2007). These catalysts were imidazolyl-functiona-lized peptides, which demonstrate a greater rate of 2,4-dinitrophenyl acetate hydrolysis when immobilized on the peptide amphiphile than the rate observed when the same enzyme is present in solution. Although the density of the enzymes on the fiber surface has not been established, the authors attribute the increase in enzymatic activity to the likely concentration of enzyme along the fiber surface, and this study illustrates one of the advantages of enzyme immobilization. 

The fate of peptide amphiphiles will be critical to their development as materials for in vivo use. Studies by Beniash and colleagues found that cells entrapped within a network of peptide amphiphiles internalize fibers by endocytosis and store these fibers in the lysosome. In this case the fibers displayed a KGE motif, with similar charge properties to RGD, and the cells could proliferate within these scaffolds for at least 3 weeks. Studies of glucose and lactate concentrations suggest the cell may metabolize the peptide amphiphiles (Beniash et al., 2005), indicating that clearance of these peptides from the site of application is unlikely to be an issue for these structures. 

Peptide amphiphiles may also be used for drug delivery. For example, Marini used fluorescently labeled peptide amphiphiles that were functionalized with the cyclo-RGD ligand and found that these structures were internalized by cells (Marini et al., 2002). 

All peptide and protein ion channels, as well as synthetic ion channels, are amphiphilic structures with an outer coat of nonpolar residues and a lining of polar and charged residues.89-97 These attributes are provided in a cooperative fashion by... 

Figure 8. A p -nonapetide, which has been shown to be capable of mimicking an amphiphilic a-peptidic helical structure in a pepide-protein interaction [26], was C-labeIled and injected into rats. After 24 hours (in serum, not shown) and after 4 days (in urine and in feces the minor and major secretion pathways, respectively), there was hardly any metabolism, see the HPLC chromatograms with radiodetection (DSPOl is the compound, the formula of which is shown above) [68],...

Biological molecules do show regularity at the level that is not obtained with synthetic polymers. Protein folding is a perfect example, but it is not yet well understood. Therefore, protein-based 3D drug delivery systems are difficult to design. However, small peptides with amphiphilic structure (e.g., V6K, where six valines form hydrophobic part and lysine is the hydrophilic end group) can assemble... 

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