Maleimide–thiol adducts stabilized through stretching

Huang, Wenguang; Wu, Xin; Gao, Xiang; Yu, Yifei; Lei, Hong; Zhu, Zhenshu; Shi, Yi; Chen, Yulan; Qin, Meng; Wang, Wei; Cao, Yi

doi:10.1038/s41557-018-0209-2

Cited by 189 publications

(137 citation statements)

References 62 publications

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“…1-8). The AFM-based SMFS approach has been widely used to measure adhesion of biomolecules and polymers and to analyze elastic protein topological structure, ligand recognition and polymer mechanics [30][31][32][33][34][35] . In a typical force spectroscopy experiment, the cantilevers were approached to the substrate at a constant speed of 1000 nm s −1 , held on the surface with a constant force of 0.3-0.5 nN for 2 s, and then retracted at the same speed.…”

Section: Resultsmentioning

confidence: 99%

Molecular design principles of Lysine-DOPA wet adhesion

et al. 2020

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The mussel byssus has long been a source of inspiration for the adhesion community. Recently, adhesive synergy between flanking lysine (Lys, K) and 3,4-Dihydroxyphenylalanine (DOPA, Y) residues in the mussel foot proteins (Mfps) has been highlighted. However, the complex topological relationship of DOPA and Lys as well as the interfacial adhesive roles of other amino acids have been understudied. Herein, we study adhesion of Lys and DOPAcontaining peptides to organic and inorganic substrates using single-molecule force spectroscopy (SMFS). We show that a modest increase in peptide length, from KY to (KY) 3 , increases adhesion strength to TiO 2. Surprisingly, further increase in peptide length offers no additional benefit. Additionally, comparison of adhesion of dipeptides containing Lys and either DOPA (KY) or phenylalanine (KF) shows that DOPA is stronger and more versatile. We furthermore demonstrate that incorporating a nonadhesive spacer between (KY) repeats can mimic the hidden length in the Mfp and act as an effective strategy to dissipate energy.

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Section: Resultsmentioning

confidence: 99%

Molecular design principles of Lysine-DOPA wet adhesion

et al. 2020

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“…The iRGD-lipopeptide (DSPE-PEG2000-iRGD) was synthesized by coupling iRGD peptide to DSPE-PEG2000-maleimide via Michael-type addition reaction 15 , 16 . MTX and ICG were encapsulated into the liposomes by the thin film-hydration method, and the hydrated liposomes were lyophilized for 48 h using 5% sucrose as the cryoprotectant.…”

Section: Methodsmentioning

confidence: 99%

Near-infrared fluorescence imaging-guided focused ultrasound-mediated therapy against Rheumatoid Arthritis by MTX-ICG-loaded iRGD-modified echogenic liposomes

et al. 2020

Theranostics

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Rheumatoid arthritis (RA), a common inflammatory disorder of the joints characterized by synovitis and pannus formation, often results in irreversible joint erosion and disability. Methotrexate (MTX) is the first-line drug against RA, but the therapeutic effects are sub-optimal due to its poor retention at the target sites and systemic side effects. Multifunctional nanoparticles are highly promising agents for minimally invasive, traceable and effective targeted therapy. Methods: This study developed iRGD peptide-functionalized echogenic liposomes (iELPs) which encapsulates MTX and indocyanine green (ICG) fluorescent probe through the thin film-hydration method. Results: The resulting iELPs showed high affinity for endothelial cells overexpressing αvβ3 integrin, favorable acoustic response and fluorescence tracking properties. Also, near-infrared (NIR) fluorescence imaging of iELPs and ultrasound-triggered drug release of MTX were proved in a mouse RA model, greatly improving the therapeutic efficacy and reducing MTX side effects. Histological assessment of the articular tissues further revealed significantly lower inflammatory cell infiltration and angiogenesis in the iELPs-treated and sonicated mice. Conclusion: Our study provides a promising nanoplatform for integrating ultrasound-controlled drug release and NIR fluorescence imaging for RA treatment.

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“…Spytag can bind Spycatcher to form a covalent isopeptide bond 37,38 . Unfortunately, the maximum detaching force in this design was even lower than that based on the Fgβ/SdrG interaction, presumably due to the maleimide-thiol chemistry we used for protein immobilization, which was not strong enough if the conjugate was not hydrolyzed 39 . In this covalent linking scheme, each molecule can be stretched only once, preventing the mechanically triggered hydrolysis of maleimide-thiol adducts 39 .…”

Section: Ester Bond Containing C1 Domain Is Inextensible Under Mechanmentioning

confidence: 92%

Molecular origin of the extreme mechanical strength of an ester bond containing pathogen surface protein

Lei¹,

Ma²,

Li³

et al. 2020

Preprint

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Gram-positive bacteria can resist large mechanical perturbations during their invasion and colonization by secreting various surface proteins with intramolecular isopeptide or ester bonds. Previous studies showed that the isopeptide bond containing proteins are inextensible under mechanical load. However, compared to isopeptide bonds, ester bonds are prone to hydrolysis; it remains elusive whether ester bonds play similar roles as isopetide bonds to completely block mechanical extension, or alternatively dissipate mechanical energy by bond rupture. Here, we show that an ester bond containing protein, the C1 domain of Cpe0147, is not extensible even at forces > 2 nN. The ester bond locks the structure to a partially unfolded conformation, in which the ester bond remains largely water inaccessible. This allows the ester bond to withstand considerable mechanical forces and in turn prevent complete protein unfolding. Inspired by this design principle, we engineer a disulfide mutant resistant to mechanical unfolding under reducing conditions.

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Maleimide–thiol adducts stabilized through stretching

Cited by 189 publications

References 62 publications

Molecular design principles of Lysine-DOPA wet adhesion

Molecular design principles of Lysine-DOPA wet adhesion

Near-infrared fluorescence imaging-guided focused ultrasound-mediated therapy against Rheumatoid Arthritis by MTX-ICG-loaded iRGD-modified echogenic liposomes

Molecular origin of the extreme mechanical strength of an ester bond containing pathogen surface protein

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