Photoresponsive Prion‐Mimic Foldamer to Induce Controlled Protein Aggregation

Marafon, Giulia; Crisma, Marco; Masato, Anna; Plotegher, Nicoletta; Bubacco, Luigi; Moretto, Alessandro

doi:10.1002/anie.202012995

Cited by 13 publications

(11 citation statements)

References 36 publications

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“…[41,42] To this end, more diverse peptides with different lengths, amino acid sequences and their structural and functional modulations will be tested. In addition, hydrazone-peptide hybrids for guest recognitions, catalytic reactions, [55] functional self-assembly [68][69][70] will also be explored in due course.…”

Section: Discussionmentioning

confidence: 99%

Hydrazone Photoswitches for Structural Modulation of Short Peptides

Jeong

Park

Seo

et al. 2022

Chemistry A European J

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Molecules that undergo light‐driven structural transformations constitute the core components in photoswitchable molecular systems and materials. Among various families of photoswitches, photochromic hydrazones have recently emerged as a novel class of photoswitches with superb properties, such as high photochemical conversion, spectral tunability, thermal stability, and fatigue resistance. Hydrazone photoswitches have been adopted in various adaptive materials at different length scales, however, their utilization for modulating biomolecules still has not been explored. Herein, we present new hydrazone switches that can photomodulate the structures of short peptides. Systematic investigation on a set of hydrazone derivatives revealed that installation of the amide group does not significantly alter the photoswitching behaviors. Importantly, a hydrazone switch comprising an upper phenyl ring and a lower quinolinyl ring was effective for structural control of peptides. We anticipate that this work, as a new milestone in the research of hydrazone switches, will open a new avenue for structural and functional control of biomolecules.

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Section: Discussionmentioning

confidence: 99%

Hydrazone Photoswitches for Structural Modulation of Short Peptides

Jeong

Park

Seo

et al. 2022

Chemistry A European J

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“…The diversity of chemical space can be conveniently tuned in foldamers, an essential property for the optimization of interactions with targets. Various foldamers, including Oligoquinoline (OQ)-based and photoresponsive prion-mimics have been shown to modulate the self-assembly of islet amyloid polypeptide 22 – 26 , Aβ peptide 21 , and αS 27 whose aggregation is associated with type 2 diabetes (T2D),Alzheimer’s disease (AD), and PD respectively.…”

Section: Introductionmentioning

confidence: 99%

Foldamers reveal and validate therapeutic targets associated with toxic α-synuclein self-assembly

et al. 2022

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Parkinson’s disease (PD) is a progressive neurodegenerative disorder for which there is no successful prevention or intervention. The pathological hallmark for PD involves the self-assembly of functional Alpha-Synuclein (αS) into non-functional amyloid structures. One of the potential therapeutic interventions against PD is the effective inhibition of αS aggregation. However, the bottleneck towards achieving this goal is the identification of αS domains/sequences that are essential for aggregation. Using a protein mimetic approach, we have identified αS sequences-based targets that are essential for aggregation and will have significant therapeutic implications. An extensive array of in vitro, ex vivo, and in vivo assays is utilized to validate αS sequences and their structural characteristics that are essential for aggregation and propagation of PD phenotypes. The study aids in developing significant mechanistic and therapeutic insights into various facets of αS aggregation, which will pave the way for effective treatments for PD.

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“…It has been found that Aaa (Δ Z βAla) residue in a peptide allows formation of an N-H••O = C intra-residue H-bond which closes a 6-membered pseudo ring system, allowing the peptide to form a well-de ned 3D architecture of the attened β sheet 29 . Recent studies demonstrated that foldamers containing Δ Z βAla/Δ E βAla units display interesting conformational, electronic, and supramolecular aggregation properties that can be modulated by selective E-Z photoisomerization [30][31][32] .…”

Section: Discussionmentioning

confidence: 99%

A ribosomally synthesized and post-translationally modified peptide containing a β-amino acid and a macrocyclic motif

Wang

Fang

Gyampoh

et al. 2021

Preprint

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Ribosomally synthesized and post-translationally modified peptides (RiPPs) are structurally complex naturally occurring metabolites across all three domains of life. Despite the structural diversity of RiPPs that stems from the extensive post-translational modifications, only α-amino acid residues have been found in known RiPPs. Here we report discovery of a new 27-mer peptide, kintamdin, using comprehensive MS and NMR structural elucidation and genomic analysis together with computational modelling. The peptide features a β-amino acid residue and a new thioether macrocyclic ring. Heterologous expression and gene inactivation allowed the identification of the minimal biosynthetic gene cluster (BGC). The gene products in kin BGC share low homologues compared to other known RiPP pathways, further rendering the novelty of kintamdin. Biochemical analysis indicated that KinO mediate di-methylation reaction to yield kintamidn. Finally, the occurrence of the kin-like BGCs in Gram-positive bacteria suggested the biological importance of this new group of RiPPs.

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Photoresponsive Prion‐Mimic Foldamer to Induce Controlled Protein Aggregation

Cited by 13 publications

References 36 publications

Hydrazone Photoswitches for Structural Modulation of Short Peptides

Hydrazone Photoswitches for Structural Modulation of Short Peptides

Foldamers reveal and validate therapeutic targets associated with toxic α-synuclein self-assembly

A ribosomally synthesized and post-translationally modified peptide containing a β-amino acid and a macrocyclic motif

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