Synthesis and Photochemistry of a New Class of Photocleavable Protein Cross‐linking Reagents

Milanesi, Lilia; Reid, Gavin D.; Beddard, Godfrey S.; Hunter, Christopher A.; Waltho, Jonathan P.

doi:10.1002/chem.200305405

Cited by 13 publications

(16 citation statements)

References 48 publications

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“…7−9 This caging effect will decrease the quantum yield of radical formation, but in some biologically relevant systems a 30% yield is still obtained in the absence of intrinsic structural constraints. 10 We have focused on the photoinduced dynamics of dithiane (Scheme 1), which is the smallest possible saturated cyclic structure containing an S−S bond that is stable enough to be exposed to ambient experimental conditions. This compound mimics the structural motif involving the S− S bond that stabilizes the tertiary and quaternary structure in many proteins.…”

Section: * S Supporting Informationmentioning

confidence: 99%

Surprising Intrinsic Photostability of the Disulfide Bridge Common in Proteins

et al. 2012

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For a molecule to survive evolution and to become a key building block in nature, photochemical stability is essential. The photolytically weak S−S bond does not immediately seem to possess that ability. We mapped the real-time motion of the two sulfur radicals that result from disulfide photolysis on the femtosecond time scale and found the reason for the existence of the S−S bridge as a natural building block in folded structures. The sulfur atoms will indeed move apart on the excited state but only to oscillate around the S−S center of mass. At long S−S distances, there is a strong coupling to the ground state, and the oscillatory motion enables the molecules to continuously revisit that particular region of the potential energy surface. When a structural feature such as a ring prevents the sulfur radicals from flying apart and thus assures a sufficient residence time in the active region of the potential energy surface, the electronic energy is converted into less harmful vibrational energy, thereby restoring the S−S bond in the ground state.* S Supporting Information Details of the experimental setup, electronic structure calculations, and method of fitting the experimental data. This material is available free of charge via the Internet at http://pubs.acs.org.

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Section: * S Supporting Informationmentioning

confidence: 99%

Surprising Intrinsic Photostability of the Disulfide Bridge Common in Proteins

et al. 2012

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“…Among those functionalized surfaces, the maleimide functional group is especially interesting because it is widely used for crosslinking and surface immobilization of biomolecules due to its selectivity for sulfhydryl groups under aqueous condition. To achieve this special surface, a large variety of preparation methods have been reported, Houseman prepared maleimide surface starting from a thiol self‐assembled monolayer,3 Rezania et al used N ‐(2‐aminoethyl)‐3‐aminopropyl‐trimethoxysilane (EDS) as a ligand to produce maleimide‐activated surfaces,4 Milanesi and his colleagues fabricated such surfaces using photochemistry;5 etc.…”

Section: Introductionmentioning

confidence: 99%

Infrared spectroscopic ellipsometry (IRSE) and X‐ray photoelectron spectroscopy (XPS) monitoring the preparation of maleimide‐functionalized surfaces: from Au towards Si (111)

Sun

Hovestädt

Zhang

et al. 2010

Surface & Interface Analysis

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The IR ellipsometric technique was used to identify the surface species and to control the preparation of maleimide-terminated surfaces. Because of higher s/n ratios for metallic substrates, the protocol was initially developed on Au surfaces, was later successfully transferred to technologically more relevant Si (111) substrates. The functionalized surfaces were achieved by electrochemical deposition of diazonium linker films and following chemical adsorption steps. Complementary XPS was also employed to detect the surface species in the process of preparation. The immobilization of different functional molecules was proven by interpreting the specific vibrational bands in IR spectra and additionally confirmed by XPS experiments. The surface homogeneity was investigated by FT-IR synchrotron mapping ellipsometry. This work shows that the proposed protocol is an effective pathway to achieve the desired functionalized surfaces.

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“…[34,35] Addition of NAC over 1 yielded a mixture of 2 and 3 in a 5:3 ratio; this mixture was separated by preparative reversed-phase HPLC (RP-HPLC). The water-gelating ability of 2 and 3 was readily observed when evaporating the corresponding aqueous fractions containing the gelators.…”

Section: Resultsmentioning

confidence: 99%

“…Herein we report multistimuli-responsive LMWHs based on this approach (Scheme 1); these were discovered by serendipity during the synthesis of optical triggers for the study of protein folding. [34,35] A hydrophobic disulfide bond, located in the hydrophobic part of the molecule provides reversible responsiveness to redox stimuli. [11,36,37] Hydrophilic carboxylic-acid moieties, located in the hydrophilic part of the molecule, provide reversible responsiveness to changes in pH.…”

Section: Introductionmentioning

confidence: 99%

“…The impact of these moieties may be reduced by offsetting the effect of an additional moiety, which is hydrophilic in nature, with the presence of another one, which is hydrophobic, each of them located in appropriate parts of the molecule. Herein we report multistimuli‐responsive LMWHs based on this approach (Scheme ); these were discovered by serendipity during the synthesis of optical triggers for the study of protein folding 34. 35 A hydrophobic disulfide bond, located in the hydrophobic part of the molecule provides reversible responsiveness to redox stimuli 11.…”

Section: Introductionmentioning

confidence: 99%

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Versatile Low‐Molecular‐Weight Hydrogelators: Achieving Multiresponsiveness through a Modular Design

Milanesi

Hunter

Tzokova

et al. 2011

Chemistry A European J

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Multiresponsive low-molecular-weight hydrogelators (LMWHs) are ideal candidates for the development of smart, soft, nanotechnology materials. The synthesis is however very challenging. On the one hand, de novo design is hampered by our limited ability to predict the assembly of small molecules in water. On the other hand, modification of pre-existing LMWHs is limited by the number of different stimuli-sensitive chemical moieties that can be introduced into a small molecule without seriously disrupting the ability to gelate water. Herein we report the synthesis and characterization of multistimuli LMWHs, based on a modular design, composed of a hydrophobic, disulfide, aromatic moiety, a maleimide linker, and a hydrophilic section based on an amino acid, here N-acetyl-L-cysteine (NAC). As most LMWHs, these gelators experience reversible gel-to-sol transition following temperature changes. Additionally, the NAC moiety allows reversible control of the assembly of the gel by pH changes. The reduction of the aromatic disulfide triggers a gel-to-sol transition that, depending on the design of the particular LMWH, can be reverted by reoxidation of the resulting thiol. Finally, the hydrolysis of the cyclic imide moieties provides an additional trigger for the gel-to-sol transition with a timescale that is appropriate for use in drug-delivery applications. The efficient response to the multiple external stimuli, coupled to the modular design makes these LMWHs an excellent starting point for the development of smart nanomaterials with applications that include controlled drug release. These hydrogelators, which were discovered by serendipity rather than design, suggest nonetheless a general strategy for the introduction of multiple stimuli-sensitive chemical moieties, to offset the introduction of hydrophilic moieties with additional hydrophobic ones, in order to minimize the upsetting of the critical hydrophobic-hydrophilic balance of the LMWH.

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Synthesis and Photochemistry of a New Class of Photocleavable Protein Cross‐linking Reagents

Cited by 13 publications

References 48 publications

Surprising Intrinsic Photostability of the Disulfide Bridge Common in Proteins

Surprising Intrinsic Photostability of the Disulfide Bridge Common in Proteins

Infrared spectroscopic ellipsometry (IRSE) and X‐ray photoelectron spectroscopy (XPS) monitoring the preparation of maleimide‐functionalized surfaces: from Au towards Si (111)

Versatile Low‐Molecular‐Weight Hydrogelators: Achieving Multiresponsiveness through a Modular Design

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