Factors Affecting Secondary and Supramolecular Structures of Self‐Assembling Peptide Nanocarriers

Abstract

Self-assembling peptides are a popular vector for therapeutic cargo delivery due to their versatility, tunability, and biocompatibility. Accurately predicting secondary and supramolecular structures of self-assembling peptides is essential for de novo peptide design. However, computational modeling of such assemblies is not yet able to accurately predict structure formation for many peptide sequences. This review identifies patterns in literature between secondary and supramolecular structures, primary sequences, and applications to provide a guide for informed peptide design. An overview of peptide structures, their applications as nanocarriers, and analytical methods for characterizing secondary and supramolecular structure is examined. A top-down approach is then used to identify trends between peptide sequence and assembly structure from the current literature, including an analysis of the drivers at work, such as local and nonlocal sequence effects and solution conditions.

De Novo Self-Assembling Peptides Mediate the Conversion of Temozolomide and Delivery of a Model Drug into Glioblastoma Multiforme Cells

“…Additionally, peptides assembled in water exhibited more beta-sheet formation than peptides assembled in PBS. Salts are known to act as kosmotropes or chaotropes in protein and peptide folding, causing differences in secondary structure between solvents [ 16 ]. Peptide hydrogels previously characterized in the literature, such as RADA16 and EAK16, exhibit beta-sheet secondary structures; therefore, beta-sheet structures may be indicative of hydrogel-like supramolecular assemblies [ 26 , 27 ].…”

“…Compared to polymer-based drug delivery systems, peptide-based systems are generally more biocompatible [ 14 ]. Short peptides, often consisting of alternating hydrophobic and hydrophilic regions, self-assemble in aqueous solutions to form nanoparticle, nanotube, or nanofiber structures with beta-sheet or alpha helix secondary structures [ 14 , 15 , 16 ]. Self-assembly occurs due to a combination of hydrogen bonding, Van der Waals forces, hydrophobic interactions, and ionic bonding between oppositely charged amino acids [ 17 ].…”

Self-assembling peptides as immunomodulatory biomaterials

“…By knowing the disease pathology pathways SAPs can be modified to incorporate small molecules and receptor domains to improve disease state. Although functional moieties can be incorporated into SAPs, it is difficult to precisely control and predict secondary and supramolecular structures (Scanlon, 2008;Pitz et al, 2022). Therefore, more advanced computational modeling must be developed to accurately predict the structure of self-assembling peptides (Chang et al, 2022;Pitz et al, 2022).…”

A Light Scattering Investigation of Enzymatic Gelation in Self-Assembling Peptides

“…While the micro-structure of peptide-based hydrogels, and their mechanical properties, have been extensively studied, with several techniques [ 21 , 35 , 36 ], such as rheometry [ 37 , 38 , 39 ], static small-angle scattering [ 40 , 41 ], and transmission electron microscopy [ 42 , 43 ], the kinetics of aggregation and the following gelation have been investigated much less. A relatively small number of works have investigated the assembly process using circular dichroism (CD) [ 44 , 45 , 46 , 47 ], Fourier-transform infrared spectroscopy (FTIR) [ 48 ], and thioflavin T fluorescence [ 34 , 49 ].…”