Guiding principles for peptide nanotechnology through directed discovery

Abstract

Life's diverse molecular functions are largely based on only a small number of highly conserved building blocks - the twenty canonical amino acids. These building blocks are chemically simple, but when they are organized in three-dimensional structures of tremendous complexity, new properties emerge. This review explores recent efforts in the directed discovery of functional nanoscale systems and materials based on these same amino acids, but that are not guided by copying or editing biological systems. The review summarises insights obtained using three complementary approaches of searching the sequence space to explore sequence-structure relationships for assembly, reactivity and complexation, namely: (i) strategic editing of short peptide sequences; (ii) computational approaches to predicting and comparing assembly behaviours; (iii) dynamic peptide libraries that explore the free energy landscape. These approaches give rise to guiding principles on controlling order/disorder, complexation and reactivity by peptide sequence design.

Sequence‐Optimized Peptide Nanofibers as Growth Stimulators for Regeneration of Peripheral Neurons

“…In accordance, the negatively charged SAP 8a (Table ) failed to enhance cell adhesion and growth (Figure S1, Supporting Information). In some cases, functionalities such as an Fmoc protection group (SAP 1e ) or the RGD sequence (SAP 5a to SAP 6b ) were added at the N‐ or C‐terminus to further enhance self‐assembly and possibly cell adhesion (Table ) . The peptides listed in Table were purified with high performance liquid chromatography (HPLC) and characterized by mass spectrometry and the corresponding spectra are given in Table S1 and Figure S2, Supporting Information.…”

Fibrous Aggregates of Short Peptides Containing Two Distinct Aromatic Amino Acid Residues

“…This type of aggregate can be formed by various peptides, which organize into β ‐sheet structures . Gazit and Reches proposed a mechanism behind amyloid plaque formation by β ‐amyloid, based on the finding that the shortest motif able to self‐assemble is the FF peptide . In the case of the FF dipeptide, H‐bonding between the peptide backbones and interactions between the aromatic rings drive the formation of well‐ordered nanotubes.…”

“…[22 -24] Gazit and Reches proposed a mechanism behind amyloid plaque formation by βamyloid, based on the finding that the shortest motif able to self-assemble is the FF peptide. [13,25] In the case of the FF dipeptide, H-bonding between the peptide backbones and interactions between the aromatic rings drive the formation of well-ordered nanotubes. However, application of their fibrous aggregates as biocompatible materials could be limited due to their hydrophobicity (especially FF).…”

2D Crystal Engineering of Nanosheets Assembled from Helical Peptide Building Blocks

“…Of these, peptides are extensively studied supramolecular building blocks. They possess excellent chemical diversity and predictable assembly behavior, which can be encoded through rational alterations to the primary structure . However, the intrinsic chirality of amino acids and their proclivity toward unidirectional growth through H‐bonding interactions precludes propagation in two dimensions.…”