Skip to main content
Other
Remodeling Cross-β Nanotube Surfaces with Peptide/Lipid Chimeras
NASA Publications
  • Rong Ni, Emory University
  • W. Seth Childers, Emory University
  • Kenneth I. Hardcastle, Emory University
  • Anil K. Mehta, Emory University
  • David G. Lynn, Emory University
Date of this Version
1-1-2012
Citation

Angew. Chem. 2012, 124, 6739 –6742; DOI: 10.1002/ange.201201173

Abstract

Peptide/lipid chimeras, which are generally referred to as peptide amphiphiles, array specific peptides on the surface of ordered lipid assemblies.[1] These materials are being explored as tissue scaffolds, in drug delivery, as antimicrobrials, and for biomineralization applications.[2–6] However, the increasing realization that simple peptides with high cross-β fold propensity can achieve long-range ordered arrays comparable to lipid amphiphiles has now allowed for the creation of an entirely new architectural framework. This framework not only offers precisely controlled positioning of charges and hydrophobic patches along a robust nanotube surface, but also the systematic adjustment of that spacing in a manner that to this point has been unrealized in self-assembling materials.

Peptide amphiphiles can achieve remarkable long-range order within a range of topological lipid phases.[2–6] For example, the elongated worm-like micelles have been modeled as having alkane interiors with peptide surfaces,[4] a morphology that reflects the same structural tension between head group and alkane that molds phospholipid assemblies.[5] This structure suggests that various self-assembling peptide elements might be able to extend the standard amphiphile tensions into new frameworks, and focused our attention on the strong self-organizing potential of the cross-b fold.[3, 5,7, 8] The nucleating core sequence of the amyloid forming Aβ-peptide associated with Alzheimer’s disease, Aβ(16-22), K16LVFFAE22-NH2, which organizes into diverse cross-β assemblies,[9–13] was acylated through conventional solid-phase Fmoc chemistry at the N-terminus with straight chain fatty acids ranging in length from two to sixteen carbon atoms. The products were purified by RP-HPLC, assembled under a range of conditions, and the resulting assemblies scored by electron microscopy (EM).

Of the series assembled under acidic conditions, C2 (N-acetyl) through C4 (N-butyryl) assemblies were morphologically morphologically indistinguishable (Supporting Information, Figure S1), and assigned as hollow tubes based on the previously characterized N-acetyl-Aβ(16-22) assemblies.[10] Intermediate acyl chain lengths, C5 to C10, assembled as ribbons, and longer lengths, C14 and C16, formed fibers (Supporting Information, Figure S1). Most notably however, the C11 (N-undecanoyl), C12 (N-lauroyl), and C13 (N-tridecanoyl) Aβ(16-22) chimeras appeared as homogeneous tubes most similar to the N-acetyl assemblies, with the same distinct edges that arise from negative staining by uranyl acetate deposition inside and outside the tube cavity (Figure 1b).

Citation Information
Rong Ni, W. Seth Childers, Kenneth I. Hardcastle, Anil K. Mehta, et al.. "Remodeling Cross-β Nanotube Surfaces with Peptide/Lipid Chimeras" (2012)
Available at: http://works.bepress.com/david_lynn/3/