Circular Dichroism of Peptides

Bakshi, Kunal; Liyanage, Mangala Roshan; Volkin, David B.; Middaugh, C. Russell

doi:10.1007/978-1-62703-673-3_17

Cited by 22 publications

(26 citation statements)

References 6 publications

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“…CD spectra of Aβ 1–42 , Aβ pE3-42 , and their combinations in dry form shown in Figure 2a indicate mostly α-helical structure with two minima around 222 and 208 nm. 40,41 The spectrum of Aβ pE3-42 has a significantly reduced ratio of ellipticities θ 208 /θ 222 , indicative of a more flexible or disordered α-helix. 42 These results concur with solution NMR data showing α-helical conformation for both Aβ 1–42 and Aβ pE3–40 in organic solvents.…”

Section: Resultsmentioning

confidence: 99%

Pyroglutamylated Amyloid-β Peptide Reverses Cross β-Sheets by a Prion-Like Mechanism

et al. 2014

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The amyloid hypothesis causatively relates the fibrillar deposits of amyloid β peptide (Aβ) to Alzheimer’s disease (AD). More recent data, however, identify the soluble oligomers as the major cytotoxic entities. Pyroglutamylated Aβ (pE-Aβ) is present in AD brains and exerts augmented neurotoxicity, which is believed to result from its higher β-sheet propensity and faster fibrillization. While this concept is based on a set of experimental results, others have reported similar β-sheet contents in unmodified and pyroglutamylated Aβ, and slower aggregation of pE-Aβ as compared to unmodified Aβ, leaving the issue unresolved. Here, we assess the structural differences between Aβ and pE-Aβ peptides that may underlie their distinct cytotoxicities. Transmission electron microscopy identifies a larger number of prefibrillar aggregates of pE-Aβ at early stages of aggregation and suggests that pE-Aβ affects the fibrillogenesis even at low molar fractions. Circular dichroism and FTIR data indicate that while the unmodified Aβ readily forms β-sheet fibrils in aqueous media, pE-Aβ displays increased α-helical and decreased β-sheet propensity. Moreover, isotope-edited FTIR spectroscopy shows that pE-Aβ reverses β-sheet formation and hence fibrillogenesis of the unmodified Aβ peptide via a prion-like mechanism. These data provide a novel structural mechanism for pE-Aβ hypertoxicity; pE-Aβ undergoes faster formation of prefibrillar aggregates due to its increased hydrophobicity, thus shifting the initial stages of fibrillogenesis toward smaller, hypertoxic oligomers of partial α-helical structure.

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Section: Resultsmentioning

confidence: 99%

Pyroglutamylated Amyloid-β Peptide Reverses Cross β-Sheets by a Prion-Like Mechanism

et al. 2014

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“…Circular dichroism measurements (Bakshi et al, 2014) were carried out to examine the effect of peptide on the secondary structure of S. aureus CVCC 546 gDNA at peptide/gDNA ratios of 0.5 and 1, respectively. After incubation, the mixtures were loaded and scanned from 220 to 320 nm at room temperature with a Bio-Logic MOS450 spectropolarimeter (France).…”

Section: Spectramentioning

confidence: 99%

An Enhanced Variant Designed From DLP4 Cationic Peptide Against Staphylococcus aureus CVCC 546

Yang

Wang

et al. 2020

Front. Microbiol.

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Insect defensins are promising candidates for the development of potent antimicrobials against antibiotic-resistant Staphylococcus aureus (S. aureus). An insect defensin, DLP4, isolated from the hemolymph of Hermetia illucens larvae, showed low antimicrobial activity against Gram-positive (G +) pathogens and high cytotoxicity, which limited its effective therapeutic application. To obtain more potent and low cytotoxicity molecules, a series of peptides was designed based on the DLP4 template by changing the conservative site, secondary structure, charge, or hydrophobicity. Among them, a variant designated as ID13 exhibited strong antibacterial activity at low MIC values of 4-8 µg/mL to G + pathogens (S. aureus: 4 µg/mL; Staphylococcus epidermidis: 8 µg/mL; Streptococcus pneumoniae: 4 µg/mL; Streptococcus suis: 4 µg/mL), which were lower than those of DLP4 (S. aureus: 16 µg/mL; S. epidermidis: 64 µg/mL; S. pneumoniae: 32 µg/mL; S. suis: 16 µg/mL), and cytotoxicity of ID13 (71.4% viability) was less than that of DLP4 (63.8% viability). ID13 could penetrate and destroy the cell membrane of S. aureus CVCC 546, resulting in an increase in potassium ion leakage; it bound to genomic DNA (gDNA) and led to the change of gDNA conformation. After treatment with ID13, perforated, wrinkled, and collapsed S. aureus CVCC 546 cells were observed in electron microscopy. Additionally, ID13 killed over 99.99% of S. aureus within 1 h, 2 × MIC of ID13 induced a post-antibiotic effect (PAE) of 12.78 ± 0.28 h, and 10 mg/kg ID13 caused a 1.8 log 10 (CFU/g) (CFU: colony-forming units) reduction of S. aureus in infected mouse thigh muscles and a downregulation of TNF-α, IL-6, and IL-10 levels, which were superior to those of DLP4 or vancomycin. These findings indicate that ID13 may be a promising peptide antimicrobial agent for therapeutic application.

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“…The chiral biomolecules including DNA, proteins and peptides interact with right-and left-handed photons differently, and that difference generates anon-zero CDsignal depending on the conformation of the molecules [263]. CD spectroscopy functions at the near and far UV regions (180-320 nm) and provides information onthe secondary structure of peptide assemblies [264], conformational changes that may occur following pH change [265], chirality of supramolecular peptide architectures [266] and interactions between toxic molecules [267], or metal ions [268] and selfassembling peptides. Recently, induced supramolecular chirality of achiral chromophores, whether covalently attached or noncovalently conjugated to the chiral PA molecules as a result of self-assembly, have been studied using this technique in solution phase [169].…”

Section: Spectroscopic Analysismentioning

confidence: 99%

Self-assembled peptide nanostructures for functional materials

et al. 2016

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Nature is an important inspirational source for scientists, and presents complex and elegant examples of adaptive and intelligent systems created by self-assembly. Significant effort has been devoted to understanding these sophisticated systems. The self-assembly process enables us to create supramolecular nanostructures with high order and complexity, and peptide-based self-assembling building blocks can serve as suitable platforms to construct nanostructures showing diverse features and applications. In this review, peptide-based supramolecular assemblies will be discussed in terms of their synthesis, design, characterization and application. Peptide nanostructures are categorized based on their chemical and physical properties and will be examined by rationalizing the influence of peptide design on the resulting morphology and the methods employed to characterize these high order complex systems. Moreover, the application of self-assembled peptide nanomaterials as functional materials in information technologies and environmental sciences will be reviewed by providing examples from recently published high-impact studies.

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Circular Dichroism of Peptides

Cited by 22 publications

References 6 publications

Pyroglutamylated Amyloid-β Peptide Reverses Cross β-Sheets by a Prion-Like Mechanism

Pyroglutamylated Amyloid-β Peptide Reverses Cross β-Sheets by a Prion-Like Mechanism

An Enhanced Variant Designed From DLP4 Cationic Peptide Against Staphylococcus aureus CVCC 546

Self-assembled peptide nanostructures for functional materials

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