Self-Assembly of Lipopeptides Containing Short Peptide Fragments Derived from the Gastrointestinal Hormone PYY_3–36: From Micelles to Amyloid Fibrils

Abstract

We investigate the impact of lipidation on the self-assembly of two peptide fragments from the gastrointestinal peptide hormone PYY 3−36 . The lipopeptides C 16 IKPEAP and C 16 IKPEAPGE contain the first 6 and 8 amino acid residues, respectively, from the PYY 3−36 peptide sequence, with a palmitoyl C 16 tail attached at the N-terminus. These lipopeptides form spherical micelles in aqueous solution, above a critical micelle concentration (cmc), which is pH-dependent. Modeling of smallangle X-ray scattering data along with molecular dynamics simulations shows the formation of micelles with a hydrophobic interior and a well-hydrated exterior. The lipopeptides have a disordered conformation over the pH and temperature ranges studied. The cmc is found to be independent of temperature, pointing to athermal micellization. In contrast to the presence of hydrated micelles in solution, β-sheet amyloid fibrils form in dried samples. Thus, the nanostructure of lipidated PYY 3−36 fragment peptides can be tuned by control of pH or concentration, for future applications.

Polymorphism of asymmetric catalysts based on amphiphilic lipopeptides in solution

“…As can be seen in Figure S2, the same cac value was observed for solutions with ANS (except PRWG(C18H37)2) , a probe that is well known to promote interaction with hydrophobic binding sites, enhancing the fluorescence signal. [41,42] The original fluorescence emission spectra are shown in Figures S3 and S4. It is surprising that the cac does not seem to be sensitive to the different numbers of alkyl chains in the mono-and di-alkyl chain functionalized molecules.…”

Multivalent display of chemical signals on self‐assembled peptide scaffolds

“…[175] C 16 -IKPEAP, a lipid conjugate of the N-terminal hexapeptide fragment from the human gut hormone PYY 3-36 , has recently been shown to assemble into spherical micelles in aqueous media, but form β-sheet fibrillar structures when dried. [347] This sequence was F I G U R E 1 3 A, Generic aldol condensation reaction scheme. B, Representative examples of selfassembling peptide materials that act as aldolases inverted to yield the peptide amphiphile PAEPKI-C 16 (Figure 13), which possesses a free N-terminal proline residue.…”

Melanin production by tyrosinase activity on a tyrosine-rich peptide fragment and pH-dependent self-assembly of its lipidated analogue

“…Recently, our group studied the conformation and self-assembly of the N-terminal lipidated PYY fragments IKPEAP and IKPEAPGE in comparison to the parent peptides. 10 Both the lipidated peptides form spherical micelles above pH-dependent critical micelle concentrations, however the unlipidated peptides do not show aggregation behaviour. The lipidated peptides adopt unordered conformations.…”

“…[4][5][6][7] Our group has recently been studying the conformation and self-assembly of the gut peptide hormone PYY3-36 and lipidated 8,9 and PEGylated 9 derivatives as well as and the N-terminal domain IKPEAP (GE) and its N-terminal palmitoylated derivative. 10 PYY3-36 and its derivatives are a promising target for the treatment of obesity and type II diabetes. PYY3-36 is an agonist for the Y2 receptor which is a G-protein coupled receptor.…”

“…A notable transition to amyloid-like -sheet fibrils occurs upon drying solutions of the lipopeptide micelles. 10 Here we compare the self-assembly properties and anti-cancer activity of the PYY3-36-derived peptide EELNRYY and its N-terminally palmitoylated analogue. This sequence traverses the central part of the PYY3-36 sequence including part of the -helical domain.…”