Peptide amphiphiles self-assembly

Stupp, S.I., Hulvat, J.F., and Rajangam, K. Angiogenic Heparin-Binding Epitopes, Peptide Amphiphiles, Self-Assembled Compositions and Related Methods of Use, 2006-US7864 2006096614 (2006). 

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 ... 

Some natural ion channels are believed to form amphiphilic a-helix bundles in hydrophobic lipid membranes, where the a-helices assemble with their hydrophilic parts facing each other, resulting in a hydrophilic channel. If artificial peptides that had appropriate combinations of both hydrophobic amino acid residues and hydrophobic amino acid sequences were used, the peptides would self-assemble to form a hydrophilic pathway in the lipid membrane. 

In both models facial amphiphilicity is the key factor. If the peptides are also long enough, they are able to span the entire membrane. Because of their facial amphiphilicity, self-assembly into pores is self-complementary and as a result pores can form with low aggregation numbers, typically around five monomers. As a result, the diameter of the pores formed by alpha-helical peptides are relatively small, however, sufficiently large to induce leakage of small molecules and ions, and becoming lethal for the cell. 

Type IV SAPs mimic the properties of polymeric and lipid surfactant molecules. They are amphiphilic in nature, as the leading head group is composed of at least one hydrophilic amino acid followed by a string of six identical hydrophobic amino acids to form the hydrophobic tail. At neutral pH, both the cationic and anionic amphiphiles self-assemble into tubular morphologies. These peptides first... 

Proteases of the trypsin family have recently been applied in the synthesis of peptides that self-assemble to nanofibrous structures and for preparing biomaterials. An example is the chymotrypsin-catalyzed polymerization of the amphiphilic peptide Lys-Leu-OEt to an alternating oligomer that forms a hydrogel [8]. Furthermore, ch3unotrypsin was used for the synthesis of poly-L-cysteine, a material for the selective chelation of SH-reactive metal ions. A high yield (80%) was obtained under mild reaction conditions [54]. 

Hamley IW, Ansari A, Castelletto V et al (2005) Solution self-assembly of hybrid block copolymers containing poly(ethylene glycol) and amphiphilic beta-strand peptide sequences. 

Niece KL, Hartgerink JD, Donners J et al (2003) Self-assembly combining two bioactive peptide-amphiphile molecules into nanofibers by electrostatic attraction. J Am Chem Soc 125 7146-7147... 

Anderson JM, Andukuri A, Lim DJ et al (2009) Modulating the gelation properties of self-assembling peptide amphiphiles. ACS Nano 3 3447-3454... 

Hartgerink JD, Beniash E, Stupp SI (2001) Self-assembly and mineralization of peptide-amphiphile nanofibers. Science 294 1684—1688... 

Stendahl JC, Rao MS, Guler MO et al (2006) Intermolecular forces in the self- assembly of peptide amphiphile nanofibers. Adv Fund Mater 16 499-508... 

Beniash E, Hartgerink JD, Storrie H et al (2005) Self-assembling peptide amphiphile nanofiber matrices for cell entrapment. Acta Biomater 1 387-397... 

In this chapter, we have surveyed a wide range of chiral molecules that self-assemble into helical structures. The molecules include aldonamides, cere-brosides, amino acid amphiphiles, peptides, phospholipids, gemini surfactants, and biological and synthetic biles. In all of these systems, researchers observe helical ribbons and tubules, often with helical markings. In certain cases, researchers also observe twisted ribbons, which are variations on helical ribbons with Gaussian rather than cylindrical curvature. These structures have a large-scale helicity which manifests the chirality of the constituent molecules. 

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