Lipidated peptide amphiphile

Peptide-resin assembly was performed by Fmoc solid-phase methodology. All peptide-amphiphiles were synthesized as C-terminal amides to prevent piperazine-2,5-dione formation. 62 Peptide-resins were characterized by Edman degradation sequence analysis as described previously for embedded (non-covalent) sequencing. 67 Peptide-resins were then lipidated with the appropriate (Cn)2-Glu-C2-OH tail to give the dialkyl peptide-amphiphile-resin. 

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 1 Structure of a peptide-amphiphile with triple-helical protein-like molecular architecture. Long-chain diaUQ l ester lipid tails (top left) are connected to linear peptide... 

Afonin S, Grage SL, Ieronimo M, Wadhwani P, Ulrich AS (2008) Temperature-dependent transmembrane insertion of the amphiphilic peptide PGLa in lipid bilayers observed by solid state F-19 NMR spectroscopy. J Am Chem Soc 130 16512-16514... 

Keywords Amphiphilic peptide-lipid interactions Cyclic fS-sheet structure ... 

Maleimide-functionalized peptides react quantitatively with thiols and thus with di-fatty acid substituted thioglycerol, a fact which facilitates purification of the amphiphilic lipopeptide derivatives by simple precipitation as required for separation of the excess lipid building block (Scheme 16).t163 164 167l... 

The presence of bulky, (3-branched side chains can be helix promoting or destabilizing depending on the environment. 100 The role of hydrophobic residues in helix stabilization has been studied in Ala-based peptides 106 as well as through Monte Carlo calculations. 107 The positioning of hydrophobic residues is also important. In amphiphilic helices, hydrophobic residues repeat approximately every three to four residues, such that one side of the helix is hydrophilic and one side hydrophobic. The amphiphilicity makes the peptide susceptible to helix formation in the presence of lipid-water interfaces. 108 109 ... 

Most important for the regulation of the membrane architecture are membrane potential, intracellular Ca2+ concentration, pH, changes in lipid composition due to the action of phospholipases and cell-cell coupling as well as the coupling of the membrane to the cytoskeleton and the extracellular matrix. Membrane architecture is additionally modulated by ions, lipo- and amphiphilic hormones, metabolites, drugs, lipid-binding peptide hormones, and amphitropic proteins [44]. 

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. 

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