Circular dichroism in functional quality evaluation of medicines

Yao, Han; Wynendaele, Evelien; Xu, Xiaolong; Kosgei, Anne; Spiegeleer, Bart De

doi:10.1016/j.jpba.2017.08.031

Cited by 48 publications

(27 citation statements)

References 122 publications

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“…Circular dichroism was utilized to estimate the conformation changes of bacterial gDNA caused by ID13. Native bacterial gDNA presents a B conformation, which provides a conservative CD spectrum with a positive band around 270 nm and a negative one around 245 nm (Yao et al, 2018). When exposed to ID13, precipitation in gDNA was observed, the positive band at 270 nm decreased and the negative one at 245 nm gradually disappeared.…”

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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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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“…In studies related to neurodegenerative diseases, PLL and PLGA often serve as a model of protein aggregation and fibrillogenesis. Among available techniques for the assignment of the existing secondary structures (Fourier‐transform infrared spectroscopy, CD, fluorescence spectroscopy, X‐Ray, atomic force microscopy and TEM), CD spectroscopy is often used for detecting the in vitro secondary structures of peptides and proteins involved in the development and progression of the disease and for studying factors that interfere with this process …”

Section: Resultsmentioning

confidence: 99%

Interactions of rationally designed small peptide dendrons functionalized with valine or sinapic acid with α‐helix and β‐sheet structures of poly‐l‐lysine and poly‐l‐glutamic acid

et al. 2020

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Uncontrolled protein oligomerization leading to deposition of fibrils is related to several diseases including neurodegeneration and diabetes. Involvement of natural compounds in regulation of this process has been documented. Therefore, the design and detailed study of bioinspired new molecular entities is one of the possible avenues to achieve better therapeutics. Here, we provide experimental data derived from the application of chiraloptic methods that rationally designed, bioinspired small branched peptides influenced the primary conformation of both poly-L-lysine (PLL) and poly-L-glutamic acid (PLGA) polypeptides in a structure-and concentrationdependent manner. In several cases, the circular dichroism (CD) spectra of polypeptide/dendron mixtures were considerably different from those corresponding to the individual polypeptides, in terms of significant reduction of intensity, discrete structure, and dislocation of characteristic bands. Data deconvolution suggested that compared to the individual homo-polypeptides, the resulting polypeptide/dendron complexes had a relative gain of distorted α-helix, and right-and left-hand twisted β-sheet forms, which may indicate a more diffuse structure. The electrostatic attraction and multiple hydrogen bonding between oppositely charged molecules, that is, between cationic-branched peptides and the β-sheet surface formed by anionic PLGA, might be the main cause of coaggregation that increased the variety and contribution of less ordered forms, and reduced the propensity for self-aggregation. K E Y W O R D S branched peptides, circular dichroism, fibrillation, sinapic acid, supramolecular interactions, valine

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“…For a deeper insight into the nature of duplex stability variations, we monitored the structural changes in NA complexes caused by the introduction of terminal closo-dodecaborates using circular dichroism (CD) spectroscopy [20][21][22]. This method permits to perform measurements in small amounts of material in physiological buffers and to reveal structural changes caused by additional ligands or groups or changes in environmental conditions, such as pH, temperature, and ionic strength.…”

Section: Circular Dichroism Studies Of Oligonucleotides and Their Dupmentioning

confidence: 99%

Terminal Mono- and Bis-Conjugates of Oligonucleotides with Closo-Dodecaborate: Synthesis and Physico-Chemical Properties

Новопашина

Vorobyeva

Lomzov

et al. 2020

IJMS

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Oligonucleotide conjugates with boron clusters have found applications in different fields of molecular biology, biotechnology, and biomedicine as potential agents for boron neutron capture therapy, siRNA components, and antisense agents. Particularly, the closo-dodecaborate anion represents a high-boron-containing residue with remarkable chemical stability and low toxicity, and is suitable for the engineering of different constructs for biomedicine and molecular biology. In the present work, we synthesized novel oligonucleotide conjugates of closo-dodecaborate attached to the 5′-, 3′-, or both terminal positions of DNA, RNA, 2′-O-Me RNA, and 2′-F-Py RNA oligomers. For their synthesis, we employed click reaction with the azido derivative of closo-dodecaborate. The key physicochemical characteristics of the conjugates have been investigated using high-performance liquid chromatography, gel electrophoresis, UV thermal melting, and circular dichroism spectroscopy. Incorporation of closo-dodecaborate residues at the 3′-end of all oligomers stabilized their complementary complexes, whereas analogous 5′-modification decreased duplex stability. Two boron clusters attached to the opposite ends of the oligomer only slightly influence the stability of complementary complexes of RNA oligonucleotide and its 2′-O-methyl and 2′-fluoro analogs. On the contrary, the same modification of DNA oligonucleotides significantly destabilized the DNA/DNA duplex but gave a strong stabilization of the duplex with an RNA target. According to circular dichroism spectroscopy results, two terminal closo-dodecaborate residues cause a prominent structural rearrangement of complementary complexes with a substantial shift from the B-form to the A-form of the double helix. The revealed changes of key characteristics of oligonucleotides caused by incorporation of terminal boron clusters, such as the increase of hydrophobicity, change of duplex stability, and prominent structural changes for DNA conjugates, should be taken into account for the development of antisense oligonucleotides, siRNAs, or aptamers bearing boron clusters. These features may also be used for engineering of developing NA constructs with pre-defined properties.

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Circular dichroism in functional quality evaluation of medicines

Cited by 48 publications

References 122 publications

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

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

Interactions of rationally designed small peptide dendrons functionalized with valine or sinapic acid with α‐helix and β‐sheet structures of poly‐l‐lysine and poly‐l‐glutamic acid

Terminal Mono- and Bis-Conjugates of Oligonucleotides with Closo-Dodecaborate: Synthesis and Physico-Chemical Properties

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