Sheet‐Like Assemblies of Charged Amphiphilic α/β‐Peptides at the Air–Water Interface

Abstract

There is growing interest in the design of molecules that undergo predictable self-assembly. Bioinspired oligomers with well-defined conformational propensities are attractive from this perspective, since they can be constructed from diverse building blocks, and self-assembly can be directed by the identities and sequence of the subunits. Here we describe the structure of monolayers formed at the air-water interface by amphiphilic α/β-peptides with 1:1 alternation of α- and β-amino acid residues along the backbone. Two of the α/β-peptides, one a dianion and the other a dication, were used to determine differences between self-assemblies of the net negatively and positively charged oligomers. Two additional α/β-peptides, both zwitterionic, were designed to favor assembly in a 1:1 molar ratio mixture with parallel orientation of neighboring strands. Monolayers formed by these α/β-peptides at the air-water interface were characterized by surface pressure-area isotherms, grazing incidence X-ray diffraction (GIXD), atomic force microscopy and ATR-FTIR. GIXD data indicate that the α/β-peptide assemblies exhibited diffraction features similar to those of β-sheet-forming α-peptides. The diffraction data allowed the construction of a detailed model of an antiparallel α/β-peptide sheet with a unique pleated structure. One of the α/β-peptide assemblies displayed high stability, unparalleled among previously studied assemblies of α-peptides. ATR-FTIR data suggest that the 1:1 mixture of zwitterionic α/β-peptides assembled in a parallel arrangement resembling that of a typical parallel β-sheet secondary structure formed by α-peptides. This study establishes guidelines for design of amphiphilic α/β-peptides that assemble in a predictable manner at an air-water interface, with control of interstrand orientation through manipulation of Coulombic interactions along the backbone.

Tyrosine-mediated two-dimensional peptide assembly and its role as a bio-inspired catalytic scaffold

“…By designing sequences, three-dimensional folding can be controlled, and various intermolecular forces to drive the assembly can also be directed at the atomic level. Various peptides and their derivatives have been identified as achieving interesting hierarchical architectures, including tubes [20][21][22][23][24] , fibres [25][26][27][28] , planar films [29][30][31][32][33] , ribbons 26,34 and three-dimensional networks [35][36][37][38][39] .…”

The Diverse World of Foldamers: Endless Possibilities of Self-Assembly

“…This was due to more favorable interactions of charged side chains of β 3 -hGlu and β 3 -hLys units in βEβK with the backbone macrodipole [ 221 ], with respect to those in the positional isomer βKβE and in any analogous α-peptidic monolayer [ 223 ]. By using atomic force microscopy, monolayers of the βEβK foldamer were subsequently shown to be composed of nanometer-width fibers, ordered in differently oriented domains in a globally disordered material, when transferred at low surface pressure, while micrometer-length uniformly aligned fibers were obtained transferring the foldamer at higher surface pressure, as shown in Figure 20 b [ 224 ]. In addition, when two β 3 -hLys residues (foldamer βK 2 ) or two β 3 -hGlu residues (foldamer βE 2 ) were inserted at both positions 4 and 8, different propensities to form pleated sheets were evidenced by surface pressure-area isotherms.…”

“…This was due to an increase of about 1.5 units in p K a of β 3 -hGlu side chains, which, in turn, became able to form stabilizing intermolecular H-bonds between carboxylic acid moieties. However, as deduced by means of attenuated total reflection FT-IR spectroscopy (ATR FT-IR), the rational design bestowed foldamers with the ability to self-assemble to some extent, even in the chloroform/trifluoroacetic acid 9:1 stock solutions [ 224 ].…”

Self‐assembly of azide containing dipeptides

“…The structures formed by the self‐assembled peptides include tubular structures, spheres, tapes, sheet‐like assemblies, and fibers . The fibers in some cases generate a fibril mesh that yields a hydrogel .…”