Self-Assembly of the Synthetic Polymer (Leu-Glu)_n:  An Amyloid-like Structure Formation

Abstract

Self-assembly of β-sheet domains resulting in the formation of pathogenic fibrillar protein aggregates (amyloids) is the causative factor in Alzheimer's, Huntington's, and Creutzfeldt-Jakob diseases. Even though different kinds of protein sequences are known to form toxic structures (amyloids), the underlying mechanism whereby protein aggregation leads to amyloid structure formation is yet to be explained clearly. In this investigation, we have shown that a simple polypeptide, poly(Leu-Glu), on aging in an aqueous solution undergoes structural transition from the soluble monomeric form to amyloid structured aggregates. Water-soluble poly(Leu-Glu) peptide slowly self-assembles into fibrillar structures as evidenced by Fourier transform infrared and circular dichroism spectroscopic methods and thioflavin T binding assay. The polypeptide underwent conformational change from a structure with a mixture of coil & turn to a macromolecular β-sheet conformation and formed amyloid-like fibrils. The fibrils were examined by Congo red staining and transmission electron microscopy. The results indicate that transition from a disordered to an ordered tertiary structure consists of both fundamental helical turns and β-sheet repeats. The comprehensive spectroscopic and microscopic studies suggest that synthetic poly(Leu-Glu) is capable of forming an amyloid-like structure.

Solvent Microenvironments and Copper Binding Alters the Conformation and Toxicity of a Prion Fragment

“…A gradual loss of random coil structure over time, commensurate with the gain in β-sheet structure, was observed during the process of structural transition (Table 1). In the past, we have observed similar structural transitions for other amyloid forming peptides [35,46,47,48,49,50]. Such transitions are well-known in other amyloid aggregates that are associated with protein conformational diseases [51,52,53,54,55].…”

Affinity-Based Screening of Peptides Recognizing Assembly States of Self-Assembling Peptide Nanomaterials

“…In order to further investigate the strong binding and high selectivity of p01, the secondary structures of the peptides were analyzed by ATR/IR. IR spectra of the amide I region (1600−1700 cm −1 ), which is primarily assigned to CO stretching, was attributed to parallel β-sheet (1620−1640 cm −1 ), α-helix (1648−1655 cm −1 ) and antiparallel β-sheet (1670−1690 cm −1 ) . The spectra of FI nanofibers with and without p01 are shown in Figure a.…”

Cell-adhesive hydrogels composed of peptide nanofibers responsive to biological ions

“…To investigate the effect of Glu conjugation, the secondary structures of the peptides were analyzed by attenuated total reflection-IR. IR spectra of the amide I region (1600-1700 cm À1 ), which is primarily assigned to C ¼ O stretching, was attributed to b-sheet (1620-1640 cm À1 ), a-helix (1648-1655 cm À1 ) and antiparallel b-sheet (1670-1690 cm À1 ) [25][26][27] structures. The IR spectra of Y9 (Ac-YEYKYEYKY-NH 2 ) and Glu-conjugated Y9 (EnY9, n ¼ 1, 2, 3, or 4) nanofibers are shown in Figure 1.…”