Low Molecular Weight Nucleoside Gelators: A Platform for Protein Aggregation Inhibition

Johnson, Litty; Surikutchi, Bhanu Teja; Allen, Stephanie; Zelzer, Mischa; Marlow, Maria

doi:10.1021/acs.molpharmaceut.8b01013

Cited by 3 publications

(1 citation statement)

References 43 publications

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“…That is why many known procedures for inhibiting protein aggregation rely on the blocking of β-sheet contacts and promoting helix formation. For this purpose, various chemical aids are used, such as small molecule-based colloidal nanoparticles [12], steroid−quinoline hybrids [13], low molecular weight nucleoside gelators [14] and native polysaccharides [15]. Understanding the factors that control the integrity of protein aggregates requires systematic study of relevant model systems.…”

Section: Introductionmentioning

confidence: 99%

Sulfated Polysaccharides as a Fighter with Protein Non-Physiological Aggregation: The Role of Polysaccharide Flexibility and Charge Density

Makshakova,

Bogdanova,

Faizullin

et al. 2023

IJMS

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Proteins can lose native functionality due to non-physiological aggregation. In this work, we have shown the power of sulfated polysaccharides as a natural assistant to restore damaged protein structures. Protein aggregates enriched by cross-β structures are a characteristic of amyloid fibrils related to different health disorders. Our recent studies demonstrated that model fibrils of hen egg white lysozyme (HEWL) can be disaggregated and renatured by some negatively charged polysaccharides. In the current work, using the same model protein system and FTIR spectroscopy, we studied the role of conformation and charge distribution along the polysaccharide chain in the protein secondary structure conversion. The effects of three carrageenans (κ, ι, and λ) possessing from one to three sulfate groups per disaccharide unit were shown to be different. κ-Carrageenan was able to fully eliminate cross-β structures and complete the renaturation process. ι-Carrageenan only initiated the formation of native-like β-structures in HEWL, retaining most of the cross-β structures. In contrast, λ-carrageenan even increased the content of amyloid cross-β structures. Furthermore, κ-carrageenan in rigid helical conformation loses its capability to restore protein native structures, largely increasing the amount of amyloid cross-β structures. Our findings create a platform for the design of novel natural chaperons to counteract protein unfolding.

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Section: Introductionmentioning

confidence: 99%

Sulfated Polysaccharides as a Fighter with Protein Non-Physiological Aggregation: The Role of Polysaccharide Flexibility and Charge Density

Makshakova,

Bogdanova,

Faizullin

et al. 2023

IJMS

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Heterocycle‐modified 2′‐Deoxyguanosine Nucleolipid Analogs Stabilize Guanosine Gels and Self‐assemble to Form Green Fluorescent Gels

Walunj

Srivatsan

2021

Chemistry An Asian Journal

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Nucleoside-lipid conjugates are very useful supramolecular building blocks to construct self-assembled architectures suited for biomedical and material applications. Such nucleoside derivatives can be further synthetically manipulated to endow additional functionalities that could augment the assembling process and impart interesting properties. Here, we report the design, synthesis and selfassembling process of multifunctional supramolecular nucleolipid synthons containing an environment-sensitive fluorescent guanine. The amphiphilic synthons are composed of an 8-(2-(benzofuran-2-yl)vinyl)-guanine core and alkyl chains attached to 3'-O and 5'-O-positions of 2'-deoxyguanosine. The 2-(benzofuran-2-yl)vinyl (BFV) moiety attached at the C8 position of the nucleobase adopted a syn conformation about the glycosidic bond, which facilitated the self-assembly process through the formation of a G-tetrad as the basic unit. While 3',5'-diacylated BFV-modified dG analog stabilized the guanosine hydrogel by hampering the crystallization process and imparted fluorescence, BFV-modified dGs containing longer alkyl chains formed a green fluorescent organogel, which transformed into a yellow fluorescent gel in the presence of a complementary non-fluorescent cytidine nucleolipid. The ability of the dG analog containing short alkyl chains to modulate the mechanical property of a gel, and interesting fluorescence properties and self-assembling behavior exhibited by the dG analogs containing long alkyl chains in response to heat and complementary base underscore the potential use of these new supramolecular synthons in material applications.

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Mechanistic investigations into the encapsulation and release of small molecules and proteins from a supramolecular nucleoside gel in vitro and in vivo

Zelzer

Márkus

Paraskevopoulou

et al. 2020

Journal of Controlled Release

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Low Molecular Weight Nucleoside Gelators: A Platform for Protein Aggregation Inhibition

Cited by 3 publications

References 43 publications

Sulfated Polysaccharides as a Fighter with Protein Non-Physiological Aggregation: The Role of Polysaccharide Flexibility and Charge Density

Sulfated Polysaccharides as a Fighter with Protein Non-Physiological Aggregation: The Role of Polysaccharide Flexibility and Charge Density

Heterocycle‐modified 2′‐Deoxyguanosine Nucleolipid Analogs Stabilize Guanosine Gels and Self‐assemble to Form Green Fluorescent Gels

Mechanistic investigations into the encapsulation and release of small molecules and proteins from a supramolecular nucleoside gel in vitro and in vivo

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