Effect of disulphide loop length on mechanochemical structural stability of macromolecules

Wang, Feng; Diesendruck, Charles E.

doi:10.1039/c9cc07439b

Cited by 21 publications

(17 citation statements)

References 49 publications

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“…[25] In principle,formation of adisulfide within ap rotein fold could force the dihedral angles of both the S À Sb ond and the Cys side chains into strained conformations that could generate internal strain that is strong enough to tear the disulfide bond. [18] Interestingly,the successful synthetic order in this study perfectly matches the previously elucidated order of disulfide bonds formation in EETI-II during the natural folding process. [23] We therefore hypothesize,when forming the wrong intermediate this could lead to internal mechanical forces that lead to disulfide cleavage or/and unfavored structures that have low solubility.…”

Section: Resultssupporting

confidence: 85%

“…In case that internal mechanical forces overcomes the strength of the SÀSbond, this could lead to peptide cleavage and subsequent uncontrolled disulfide bonds formation. [18] In the oxidative folding approach, the presence of redox and oxidizing agents enables the system to repair itself under thermodynamic control, once the disulfide bond is formed in the wrong order,i fn oa ggregates or kinetically trapped intermediates are already formed. [10] In contrast, in the stepwise approach it could be critical to carefully design the order of disulfide formation due to absence of repair mechanism.…”

Section: Introductionmentioning

confidence: 99%

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Insight on the Order of Regioselective Ultrafast Formation of Disulfide Bonds in (Antimicrobial) Peptides and Miniproteins

et al. 2021

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Disulfide-rich peptides and proteins are among the most fascinating bioactive molecules.T he difficulties associated with the preparation of these targets have prompted the development of various chemical strategies.N evertheless,t he production of these targets remains very challenging or elusive. Recently,w ei ntroduced as trategy for one-pot disulfide bond formation, tackling most of the previous limitations.However, the effect of the order of oxidation remained an underexplored issue.Herein we report on the complete synthetic flexibility of the approach with respect to the order of oxidation of three disulfide bonds in targets that lack the knot motif.Incontrast, our study reveals an essential order of disulfide bond formation in the EETI-II knotted miniprotein. This synthetic strategy was applied for the synthesis of novel analogues of the plectasin antimicrobial peptide with enhanced activities against methicillin-resistant Staphylococcus aureus (MRSA), an otorious human pathogen.

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Section: Resultssupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Insight on the Order of Regioselective Ultrafast Formation of Disulfide Bonds in (Antimicrobial) Peptides and Miniproteins

et al. 2021

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“…Previously, loop-forming structures based on hydrogen-bonding motifs have been exploited to mimic the response of the muscle protein titin, [23] as mechanophores based on charge-transfer interactions, [24] and to investigate preferential covalent bond rupture by ultrasound or single-molecule force spectroscopy. [25] Chen et al reported that excimer emission was predominant when ad iacrylate-terminated motif featuring two excimer-forming PDIs connected by as hort bridge was used to cross-link poly(methylacrylate). [26] Swelling with dichloromethane (DCM) led to ac hange of the dominant emission color from orange to green, suggesting that the expansion of the cross-linked network disrupted the dye aggregates.…”

Section: Introductionmentioning

confidence: 99%

Folded Perylene Diimide Loops as Mechanoresponsive Motifs

et al. 2021

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A supramolecular mechanophore that can be integrated into polymers and indicates deformation by a fluorescence color change is reported. Two perylene diimides (PDIs) were connected by a short spacer and equipped with peripheral atom transfer polymerization initiators. In the idle state, the motif folds into a loop and its emission is excimer dominated. Poly(methyl acrylate) (PMA) chains were grown from the motif and the mechanophore‐containing polymer was blended with unmodified PMA to afford materials that display a visually discernible fluorescence color change upon deformation, which causes the loops to unfold. The response is instant, and correlates linearly with the applied strain. Experiments with a reference polymer containing only one PDI moiety show that looped mechanophores that display intramolecular excimer formation offer considerable advantages over intermolecular dye aggregates, including a concentration‐independent response, direct signaling of mechanical processes, and a more pronounced optical change.

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“…[16,17] Va rious design principles influence mechanochemical reactivity including the location of mechanophores, [18] regio-and stereochemistry, [19][20][21][22][23] linkers, [24][25][26] polymer composition, [27,28] and polymer topology. [29] In regard to topology,i ntramolecularly cross-linked, [30][31][32][33][34] cyclic, [35] dendritic, [36,37] star, [38][39][40][41][42][43] bottlebrush, [44][45][46] and dendronized polymers, [47] have been utilized to tune mechanochemical reaction kinetics and/or mechanophore activation efficiency. Them ajority of these topology studies have been conducted using ultrasonication (US) or, to alesser extent, ball-mill grinding (BMG).…”

Section: Introductionmentioning

confidence: 99%

Mechanochemical Reactivity of Bottlebrush and Dendronized Polymers: Solid vs. Solution States

2021

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We explored the mechanochemical degradation of bottlebrush and dendronized polymers in solution (with ultrasonication, US) and solid states (with ball-mill grinding, BMG). Over 50 polymers were prepared with varying backbone length and arm architecture,composition, and size.With US,w ef ound that bottlebrush and dendronized polymers exhibited consistent backbone scission behavior,w hichw as related to their elongated conformations in solution. Considerably different behavior was observed with BMG,a sa rm architecture and composition had as ignificant impact on backbone scission rates.A rm scission was also observed for bottlebrush polymers in both solution and solid states,but only in the solid state for dendronized polymers.Motivated by these results,m ulti-mechanophore polymers with bottlebrush and dendronized polymer architectures were prepared and their reactivity was compared. Although dendronized polymers showed slower arm-scission, the selectivity for mechanophore activation was muchh igher.O verall, these results have important implications to the development of new mechanoresponsive materials.

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Effect of disulphide loop length on mechanochemical structural stability of macromolecules

Abstract: Polymer chains folded with a single disulphide loop are shown to present distinct rates of mechanochemical fragmentation.

Cited by 21 publications

References 49 publications

Insight on the Order of Regioselective Ultrafast Formation of Disulfide Bonds in (Antimicrobial) Peptides and Miniproteins

Insight on the Order of Regioselective Ultrafast Formation of Disulfide Bonds in (Antimicrobial) Peptides and Miniproteins

Folded Perylene Diimide Loops as Mechanoresponsive Motifs

Mechanochemical Reactivity of Bottlebrush and Dendronized Polymers: Solid vs. Solution States

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