498-02-2Relevant articles and documents
UV cell stress induces oxidative cyclization of a protective reagent for DNA damage reduction in skin explants
Liu, Jing,Zhu, Haizhou,Premnauth, Gurdat,Earnest, Kaylin G.,Hahn, Patricia,Gray, George,Queenan, Jack A.,Prevette, Lisa E.,AbdulSalam, Safnas F.,Kadekaro, Ana Luisa,Merino, Edward J.
, p. 133 - 138 (2019)
UV irradiation is a major driver of DNA damage and ultimately skin cancer. UV exposure leads to persistent radicals that generate ROS over prolonged periods of time. Toward the goal of developing long-lasting antioxidants that can penetrate skin, we have designed a ROS-initiated protective (RIP) reagent that, upon reaction with ROS (antioxidant activity), self-cyclizes and then releases the natural product apocynin. Apocynin is a known antioxidant and inhibitor of NOX oxidase enzymes. A key phenol on the compound 1 controls ROS-initiated cyclization and makes 1 responsive to ROS with a EC50 comparable to common antioxidants in an ABTS assay. In an in vitro DNA nicking assay, the RIP reagent prevented DNA strand breaks. In cell-based assays, the reagent was not cytotoxic, apocynin was released only in cells treated with UVR, reduced UVR-induced cell death, and lowered DNA lesion formation. Finally, topical treatment of human skin explants with the RIP reagent reduced UV-induced DNA damage as monitored by quantification of cyclobutane dimer formation and DNA repair signaling via TP53. The reagent was more effective than administration of a catalase antioxidant on skin explants. This chemistry platform will expand the types of ROS-activated motifs and enable inhibitor release for potential use as a long-acting sunscreen.
Discovery, Biocatalytic Exploration and Structural Analysis of a 4-Ethylphenol Oxidase from Gulosibacter chungangensis
Alvigini, Laura,Fraaije, Marco W.,Gran-Scheuch, Alejandro,Guo, Yiming,Mattevi, Andrea,Saifuddin, Mohammad,Trajkovic, Milos
, p. 3225 - 3233 (2021/10/04)
The vanillyl-alcohol oxidase (VAO) family is a rich source of biocatalysts for the oxidative bioconversion of phenolic compounds. Through genome mining and sequence comparisons, we found that several family members lack a generally conserved catalytic aspartate. This finding led us to study a VAO-homolog featuring a glutamate residue in place of the common aspartate. This 4-ethylphenol oxidase from Gulosibacter chungangensis (Gc4EO) shares 42 % sequence identity with VAO from Penicillium simplicissimum, contains the same 8α-N3-histidyl-bound FAD and uses oxygen as electron acceptor. However, Gc4EO features a distinct substrate scope and product specificity as it is primarily effective in the dehydrogenation of para-substituted phenols with little generation of hydroxylated products. The three-dimensional structure shows that the characteristic glutamate side chain creates a closely packed environment that may limit water accessibility and thereby protect from hydroxylation. With its high thermal stability, well defined structural properties and high expression yields, Gc4EO may become a catalyst of choice for the specific dehydrogenation of phenolic compounds bearing small substituents.
Thio-assisted reductive electrolytic cleavage of lignin β-O-4 models and authentic lignin
Fang, Zhen,Flynn, Michael G.,Jackson, James E.,Hegg, Eric L.
, p. 412 - 421 (2021/01/28)
Avoiding the use of expensive catalysts and harsh conditions such as elevated temperatures and high pressures is a critical goal in lignin depolymerization and valorization. In this study, we present a thio-assisted electrocatalytic reductive approach using inexpensive reticulated vitreous carbon (RVC) as the working cathode to cleave the β-O-4-type linkages in keto aryl ethers. In the presence of a pre-electrolyzed disulfide (2,2′-dithiodiethanol) and a radical inhibitor (BHT) at room temperature at a current density of 2.5 mA cm-2, cathodic reduction of nonphenolic β-O-4 dimers afforded over 90% of the corresponding monomeric C-O cleavage products in only 1.5 h. Extended to DDQ-oxidized poplar lignin, this combination of electric current and disulfide, applied over 6 h, released 36 wt% of ethyl acetate soluble fragments and 26 wt% of aqueous soluble fragments, leaving only 38 wt% of insoluble residue. These findings represent a significant improvement over the current alone values (24 wt% ethyl acetate soluble; 22 wt% aqueous soluble; 54 wt% insoluble residue) and represent an important next step in our efforts to develop a mild electrochemical method for reductive lignin deconstruction.
