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Photostabilizers have been used to impart stability to an FDA‐approved chemical UV‐A filter avobenzone against the UV‐A radiations and sunlight. The thiol group of glutathione plays a critical role in imparting the photostabilization activity of glutathione on avobenzone. The current report aims to evaluate the photostabilization activity of multiple thiols containing cysteine peptides on avobenzone. Cysteine‐tripeptide and cysteine‐pentapeptide were chemically synthesized and characterized using mass spectrometry. Synthetic peptides were assessed for their photostabilization activity on the enolic‐form of the avobenzone under natural sunlight using UV spectroscopy in both protic and aprotic solvents. Unlike glutathione, which has pronounced activity in protic solvents, cysteine‐pentapeptide exhibits similar photoprotection activity in both protic and aprotic solvents. Computational calculations using DFT suggest that peptide cysteine thiols may assist in the reversal of the photoketonization process of avobenzone thereby exhibiting the photoprotection activity to the enolic‐form of avobenzone. Peptide cysteine thiols lower the activation energy barrier of keto‐to‐enol tautomerization of avobenzone by 30 kcal mol−1 by assisting the proton shuttle through a six‐membered transition state. The current report emphasizes the applications of peptide thiols in cosmetics and may help in the development of peptides as aesthetic medicines. [ABSTRACT FROM AUTHOR]

Mitigation of the activity of the main protease (Mpro) and papain-like protease (PLpro) of SARS CoV-2 has direct implications in combating the ongoing deadly COVID-19 pandemic. The active site of these proteases contains cysteine thiols which are covalently modified by the sulfur drugs such as ebselen and disulfiram. The natural product of Allium contains several reactive sulfur compounds that may covalently modify the active site cysteine thiols of coronavirus proteases. The report has assessed the binding affinity of the 52 different sulfur compounds of Allium against both Mpro and PLpro of coronavirus by conventional docking methods. Three of the top six compounds have demonstrated high affinity for both the proteases, namely, E-ajoene (S3), S-(3-pentanyl)-L-cysteine-sulfoxide (S49), and 1-propenyl allyl thiosulfinate (S14). The reactive sulfur compounds E-ajoene and 1-propenyl allyl thiosulfinate were subjected to the calculation of energetics of the putative reactions and covalent docking studies. The results indicate they covalently modify the active site cysteine thiols of the proteases through S-thioallylation, S-thioallyl sulfinyl propenylation, and S-thiopropenylation. The diversity of covalent modifications, high affinity for both the proteases and sulfur-mediated hydrogen bonds at the active site indicate that E-ajoene is a potential dual protease targeting covalent inhibitor of SARS CoV-2. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is an ongoing pandemic caused due to new coronavirus infection with 3716075 deaths across the world as reported by the World Health Organization (WHO). SARS-CoV-2 main protease (Mpro) plays a vital role in the replication of coronavirus and thus an attractive target for the screening of inhibitors for the therapy of COVID-19. The preclinical drugs ebselen and PX-12 are potent inhibitors of SARS-CoV-2 Mpro and covalently modifies the active site Cys-145 residue of Mpro through selenosulfide/disulfide. In the current report, using virtual screening methods, reactive sulfur species allicin is subjecting for covalent docking at the active site of SARS-CoV-2 Mpro using PX-12 as a benchmark reference compound. The results indicate that allicin induces dual S-thioallylation of Cys-145 and Cys-85/ Cys-156 residues of SARS-CoV-2 Mpro. Using density functional theory (DFT), Gibbs free energy change (DG) is calculated for the putative reactions between N-acetylcysteine amide thiol and allicin/allyl sulfenic acid. The overall reaction is exergonic and allyl disulfide of Cys-145 residue of Mpro is involved in a sulfur mediated hydrogen bond. The results indicate that allicin causes dual S-thioallylation of SARS-CoV-2 Mpro which may be of interest for treatment and attenuation of ongoing coronavirus infection. [ABSTRACT FROM AUTHOR]

The evolution of miniature conopeptide Li520 (COWC*, *: C-terminal amidation) to exhibit the disulfide isomerase activity was probed using structure, function, disulfide conformation, and the precursor gene sequence. The peptides Li520, Li504, [O2A]Li520, [W3A]Li520, and Grx506, homologues active-site motif of glutaredoxin, were chemically synthesized and assessed for their disulfide reduction potential, intrinsic folding of disulfides, and disulfide isomerization activity on α-conotoxin ImI. The reduction potential of the disulfide of peptides varies from -189 to -344 mV, which is within the range observed for the redox family of proteins that modulates the folding of protein disulfides. The oxidative folding studies confirm the significance of the tryptophan residue in engaging Li520 in disulfide-exchange reactions and the role of proline hydroxylation in extending the lifetime of Li520 in a reduced free thiol state. Studies of quenching of tryptophan fluorescence by the disulfide in situ folding reaction in conjunction with the optimized structures by density functional theory (DFT) confirm the difference in conformation of disulfides between the native and mutant peptides. Interestingly, the native peptide Li520/Li504 shares a similar disulfide conformation of (-,-)AntiRHHook with the redox family of proteins known to modulate disulfides, particularly in lieu of the tetrapeptide of glutaredoxin, deviating from its disulfide conformation compared to its naive protein. Analysis of the precursor gene sequences of M-superfamily conotoxins revealed the presence of Li520 in different cone snail species with distinct food habits and possible modes of evolution through the diversification of cysteine motifs. The results of the report suggest that the short redox conopeptide Li520 has evolved to facilitate the oxidative folding of conotoxins and may be useful to develop as reagents for the synthesis of therapeutically important cysteine-rich peptides., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)