Controlling the Formation of Peptide Films: Fully Developed Helical Peptides are Required to Obtain a Homogenous Coating over a Large Area

Abstract

The influence of conformational dynamics on the self‐assembly process of a conformationally constrained analogue of the natural antimicrobial peptide Trichogin GA IV was analysed by spectroscopic methods, microscopy imaging at nanometre resolution, and molecular dynamics simulations. The formation of peptide films at the air/water interface and their deposition on a graphite or a mica substrate were investigated. A combination of experimental evidence with molecular dynamics simulation was used to demonstrate that only the fully developed helical structure of the analogue promotes formation of ordered aggregates that nucleate the growth of micrometric rods, which give rise to homogenous coating over wide regions of the hydrophilic mica. This work proves the influence of helix flexibility on peptide self‐organization and orientation on surfaces, key steps in the design of bioinspired organic/inorganic hybrid materials.

Peptide Self-Assembled Nanostructures: From Models to Therapeutic Peptides

“…The observation that a single amino acid substitution is able to inhibit the formation of amyloid fibrils paves the way for the design of new-concept therapeutic peptides fighting neurodegenerative diseases [ 83 ]. This effect was verified also in the formation of Langmuir–Blodgett films of model [ 91 ] and antimicrobial [ 99 ] peptides, where we demonstrated that the homogeneous coating of large areas of solid substrates is facilitated when fully developed peptide helices are used. The strategy behind the case studies discussed in this contribution is based on the restriction of the conformational landscape of the peptide building blocks with the aim to reduce the entropy penalty associated with the formation of aggregates in solution or thin films at the air/liquid interface.…”

“…To analyze the influence of the dynamical properties of TrGA on the processes that lead to the formation of the LB films, we synthesized a conformationally constrained TrGA analogue, characterized by the substitution of the Gly residues at positions 2, 5, and 16 with hydrophobic Leu residues. The Gly residue at position 9 was also suppressed [ 99 ]. These changes severely restrain the conformational region accessible to the trichogin analogue, denoted in the following as TrGAr.…”

Modulated Fluorescence in LB Films Based on DADQs—A Potential Sensing Surface?

“…LB films can be engineered for numerous applications including functional coatings, sensing surfaces, etc. [1][2][3][4][5][6][7][8][9][10][11], but LB films also resemble naturally occurring biological cell membranes. Despite widespread applications, there are, to our knowledge, very few examples of fluorescent LB films.…”

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

“…Additionally, oligomers built using exclusively non-standard α-amino acids, or a mixture of proteinogenic and non-proteinogenic α-residues, have been almost completely excluded from this review, albeit their interesting studies sometimes included the use of peculiar experimental techniques. For instance, this exclusion applies to α-peptides containing mainly α-aminoisobutyric acid (Aib), for which only a few illustrative examples have been reported here, [ 34 ] and chiral α-dialkyl α-amino acids (e.g., synthetic derivatives of naturally-occurring peptaibiotics and peptaibols [ 35 , 36 , 37 ]), whose self-assembly has been thoroughly studied [ 38 , 39 , 40 ], especially in the presence of phospholipid membranes [ 41 ], as shown in Figure 3 d, and to low-molecular-weight gelators (LMWGs) based on short α-peptide derivatives [ 42 , 43 , 44 ] or pseudopeptides [ 45 , 46 ], which do not fulfill the foldamer definition adopted here. In addition, oligomers made only of different pseudoproline units (L-pyroglutamic acid, L- p Glu, trans -4-carboxybenzyl-5-methyloxazolidin- 2-one, L- or D-Oxd, and (4 R )-(2-oxo-1,3-oxazolidin-4-yl)-acetic acid, D-Oxac), as shown in Figure 3 e, which are sometimes included in the field of foldamers, have been excluded here [ 47 ].…”