Fmoc–RGDS based fibrils: atomistic details of their hierarchical assembly

Abstract

The interaction between morphine (MO), a very potent analgesic psychoactive drug, and five electroactive polymers, poly(3,4-ethylenedioxythiophene) (PEDOT), poly(3-methylthiophene) (P3MT), polypyrrole (PPy), poly(N-methylpyrrole (PNMPy) and poly[N-(2-cyanoethyl)pyrrole] (PNCPy), has been examined using theoretical calculations on model complexes and voltammetric measures considering different pHs and incubation times. Quantum mechanical calculations in model polymers predict that the strength of the binding between the difference polymers and morphine increases as follows: PEDOT < PNMPy < PPy << P3MT ≈ PNCPy. The most relevant characteristic of P3MT is its ability to interact with morphine exclusively through non-directional interactions. On the other hand, the variations of the electroactivity and the anodic current at the reversal potential evidence that the voltammetric response towards the presence of MO is considerably higher for P3MT and PNCPy than that for the other polymers at both acid (P3MT > PNMPy) and neutral (P3MT ≈ PNCPy) pHs. Energy decomposition analyses of the interaction of MO with different model polymers indicate that the stronger affinity of MO for P3MT and PNCPy as compared to PEDOT, PNMPy, and PPy is due to more favorable orbital interactions. These more stabilizing orbital interactions are the result of the larger charge transfer from MO to P3MT and PNCPy model polymers that takes place because of the higher stability of the single occupied molecular orbital (SOMO) of these model polymers. Therefore, to design polymers with a large capacity to detect MO we suggest looking at polymers with high electron affinity.3

Amyloid‐Like Fibrillary Morphology Originated by Tyrosine‐Containing Aromatic Hexapeptides

“…WAXS diffraction patterns recorded on the dried fibers of (FY)3 and Y6 showm eridional and equatorial reflections at 4.7 and 12.5 ,r espectively.T his diffraction pattern is similar to patterns typically observed in cross-b amyloid-like structures. MD simulations, which represent ap owerful tool to obtaina tomic-level representation on self-assembling systems, [40] confirmed the capability of Tyr-rich peptides to form cross-b structures characterized by stable anhydrous interfaces, in which the intersheet distances of both the Phe-and Tyr-interface at~12.5 are in good agreement with experimental WAXS data. These interfacesa re stabilized by both stacking interactions and H-bonding pattern.…”

“…The high propensity of Phe-based oligopeptides to self-assemble hasb een investigated in many literature studies. [9][10][11][12][13] Indeed, the discoveryt hat the FF homodimer, ac ore motif in Ab 40 and Ab 42 peptides, is able to self-assemble in well-ordered nanostructures at high morphological variability, [9] has stimulated the use of FF and its variants as biocompatibleb uilding blocks for the development of novel nanostructures. In this scenario, it has been shownt hat the elongation of this aromatic framework from two to four or to six residues favors the progressive increase of b-structures in solutions.…”

Scrolling of Supramolecular Lamellae in the Hierarchical Self-Assembly of Fibrous Gels

“…38 Folding of lamellae can also be driven by the formation of hydrogen bonds or p-p stacking motifs, given that contraction of the sheet on the convex face reduces the distance between interacting moieties. 56,61 The direction of folding and radius of curvature are dictated by the stiffness of the sheet, 62 and the sizes and solvent affinities of the tether coils. Whereas rigid sheets are unable to bend, those with smaller bending and tensile moduli can undergo both local and global deformation to produce crumpled, tubular, and spheroidal morphologies.…”

“…65 Alternatively, the computational task could be simplified by comparison of the simulated dynamics of pre-constructed, idealized aggregates. 61,[66][67][68][69][70] Initial configurations can be justified on the basis of the geometry of the LMWG, the relative energies of model assemblies, or the arrangements of molecules in single-crystal structures. By adopting an atomistic approach and comparing the results for multiple lamellar systems, it is possible to test the impact of minor structural modifications and pinpoint the dominant contributions to the self-assembly outcome.…”

The Physical Properties and Self‐Assembly Potential of the RFFFR Peptide

“…This means that the cross‐section of the fiber consists of more than one peptide unit, and the monolayer configuration is often unstable . Another common model is the cylindrical fiber formation of peptide amphiphiles with a hydrophilic head and a hydrophobic tail . The last model consists of multidomain peptides that contain an ABA motif in which the A block is charged and repulsed by other A blocks.…”