Solid State Self-Assembly Mechanism of RADA16-I Designer Peptide

Cormier, Ashley R.; Ruiz-Orta, Carolina; Alamo, Rufina G.; Paravastu, Anant K.

doi:10.1021/bm300313h

Cited by 22 publications

(30 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…28, 54 These effects can be harnessed to engineer peptides which self-assemble under specific desired conditions or design processes which avoid undesirable structures. 55–57 One could predict how pH and ionic strength affect the stability of the assembly and whether alternative structures can be stabilized via changes in solvent conditions. Dynamic reassembly refers to the ability of RADA16-I nanofibers to spontaneously reassemble following mechanical damage, without the addition of new monomeric peptide.…”

Section: Resultsmentioning

confidence: 99%

Molecular Structure of RADA16-I Designer Self-Assembling Peptide Nanofibers

et al. 2013

Self Cite

View full text Add to dashboard Cite

The designer self-assembling peptide RADA16-I forms nanofiber matrices which have shown great promise for regenerative medicine and 3-dimensional cell culture. RADA16-I has a β-strand-promoting alternating hydrophobic/charged motif, but arrangement of β-strands into the nanofiber structure has not been previously determined. Here we present a structural model of RADA16-I nanofibers, based on solid-state NMR measurements on samples with different schemes for 13C isotopic labeling. NMR peak positions and line widths indicate an ordered structure composed of β-strands. The NMR data show that the nanofibers are composed of two stacked β-sheets stabilized by a hydrophobic core formed by alanine sidechains, consistent with previous proposals. However, the previously proposed antiparallel β-sheet structure is ruled out by 13C-13C dipolar couplings. Instead, neighboring β-strands within β-sheets are parallel, with a registry shift that allows for cross-strand staggering of oppositely charged arginine and aspartate sidechains. The resulting structural model is compared to nanofiber dimensions observed via images taken by transmission electron microscopy and atomic force microscopy. Multiple NMR peaks for each alanine sidechain were observed and could be attributed to multiple configurations of sidechain packing within a single scheme for intermolecular packing.

show abstract

Section: Resultsmentioning

confidence: 99%

Molecular Structure of RADA16-I Designer Self-Assembling Peptide Nanofibers

et al. 2013

Self Cite

View full text Add to dashboard Cite

show abstract

“…The indications of cross-β pattern, a sharp 4.7Å meridional reflection (corresponds to the distance between chains in the H-bonding direction) and a broad reflection centred at 9Å on the equator (distance between face-to-face separation of β-sheets), were observed [58]. 7.9Å may represent the interchain helical distances [59]. However, since it was specific for UV-B treated samples, it’s possible that 7.9Å represents the distance between the ends of 2 strands in different sheets during the turn.…”

Section: Resultsmentioning

confidence: 99%

UV-B induced fibrillization of crystallin protein mixtures

et al. 2017

View full text Add to dashboard Cite

Environmental factors, mainly oxidative stress and exposure to sunlight, induce the oxidation, cross-linking, cleavage, and deamination of crystallin proteins, resulting in their aggregation and, ultimately, cataract formation. Various denaturants have been used to initiate the aggregation of crystallin proteins in vitro. All of these regimens, however, are obviously far from replicating conditions that exist in vivo that lead to cataract formation. In fact, it is our supposition that only UV-B radiation may mimic the observed in vivo cause of crystallin alteration leading to cataract formation. This means of inducing cataract formation may provide the most appropriate in vitro platform for in-depth study of the fundamental cataractous fibril properties and allow for testing of possible treatment strategies. Herein, we showed that cataractous fibrils can be formed using UV-B radiation from α:β:γ crystallin protein mixtures. Characterization of the properties of formed aggregates confirmed the development of amyloid-like fibrils, which are in cross-β-pattern and possibly in anti-parallel β-sheet arrangement. Furthermore, we were also able to confirm that the presence of the molecular chaperone, α-crystallin, was able to inhibit fibril formation, as observed for ‘naturally’ occurring fibrils. Finally, the time-dependent fibrillation profile was found to be similar to the gradual formation of age-related nuclear cataracts. This data provided evidence for the initiation of fibril formation from physiologically relevant crystallin mixtures using UV-B radiation, and that the formed fibrils had several traits similar to that expected from cataracts developing in vivo.

show abstract

“…In recent years, advances in nanotechnology have led to the development of novel biocompatible nanomaterials including hemostats . One candidate is RADA16‐I, a synthetic type I self‐assembling peptide nanofiber scaffold (SAPNS) . It consists of ionic self‐complementary oligopeptides that would undergo spontaneous assembly when exposed to physiologic conditions.…”

Section: Introductionmentioning

confidence: 99%

“…1 One candidate is RADA16-I, a synthetic type I self-assembling peptide nanofi ber scaff old (SAPNS). 2,3 It consists of ionic self-complementary oligopeptides that would undergo spontaneous assembly when exposed to physiologic conditions. Th e resultant hydrogel is highly porous and provides a three-dimensional nanofi ber scaff old that can potentially facilitate axonal regrowth and repopulation.…”

Section: Introductionmentioning

confidence: 99%

Comparison between self‐assembling peptide nanofiber scaffold (SAPNS) and fibrin sealant in neurosurgical hemostasis

Wang

Sun

et al. 2015

Clinical Translational Sci

View full text Add to dashboard Cite

RADA16-I is a synthetic type I self-assembling peptide nanofi ber scaffold (SAPNS) which may serve as a novel biocompatible hemostatic agent. Its application in neurosurgical hemostasis, however, has not been explored. Although RADA16-I is nontoxic and nonimmunogenic, its intrinsic acidity may potentially provoke infl ammation in the surgically injured brain. We conducted an animal study to compare RADA16-I with fi brin sealant, a commonly used agent, with the hypothesis that the former would be a comparable alternative. Using a standardized surgical brain injury model, 30 Sprague-Dawley rats were randomized into three treatment groups: RADA16-I, fi brin sealant or gelatin sponge (control). Animals were sacrifi ced on day 3 and 42. Astrocytic and microglial infi ltrations within the cerebral parenchyma adjacent to the operative site were signifi cantly lower in the RADA16-I and fi brin sealant groups than control. RADA16-I did not cause more cellular infl ammatory response despite its acidity when compared with fi brin sealant. Immunohistochemical studies showed infi ltration by astrocytes and microglia into the fi brin sealant and RADA16-I grafts, suggesting their potential uses as tissue scaffolds. RADA16-I is a promising candidate for further translational and clinical studies that focus on its applications as a safe and effective hemostat, proregenerative nanofi ber scaffold as well as drug and cell carrier. Clin Trans Sci 2015; Volume 8: [490][491][492][493][494]

show abstract

Solid State Self-Assembly Mechanism of RADA16-I Designer Peptide

Cited by 22 publications

References 48 publications

Molecular Structure of RADA16-I Designer Self-Assembling Peptide Nanofibers

Molecular Structure of RADA16-I Designer Self-Assembling Peptide Nanofibers

UV-B induced fibrillization of crystallin protein mixtures

Comparison between self‐assembling peptide nanofiber scaffold (SAPNS) and fibrin sealant in neurosurgical hemostasis

Contact Info

Product

Resources

About