Novel Nanocombinations of l-Tryptophan and l-Cysteine: Preparation, Characterization, and Their Applications for Antimicrobial and Anticancer Activities

Tungsten oxide WO3 nanoparticles (NPs) were prepared in a form of nanosheets with homogeneous size and dimensions in one step through acid precipitation using a cation exchange column. The resulting WO3nanosheet surface was decorated with one of the two amino acids (AAs) l-tryptophan (Trp) or l-cysteine (Cys) and evaluated for their dye removal, antimicrobial, and antitumor activities. A noticeable improvement in the biological activity of WO3 NPs was detected upon amino acid modification compared to the original WO3. The prepared WO3-Trp and WO3-Cys exhibited strong dye removal activity toward methylene blue and safranin dyes with complete dye removal (100%) after 6 h. WO3-Cys and WO3-Trp NPs revealed higher broad-spectrum antibacterial activity toward both Gram-negative and Gram-positive bacteria, with strong antifungal activity toward Candida albicans. Anticancer results of the modified WO3-Cys and WO3-Trp NPs against various kinds of cancer cells, including MCF-7, Caco-2, and HepG-2 cells, indicate that they have a potent effect in a dose-dependent manner with high selectivity to cancer cells and safety against normal cells. The expression levels of E2F2 and Bcl-2 genes were found to be suppressed after treatment with both WO3-Cys and WO3-Trp NPs more than 5-FU-treated cells. While expression level of the p53 gene in all tested cells was up-regulated after treatment 5–8 folds more as compared to untreated cells. The docking results confirmed the ability of both NPs to bind to the p53 gene with relevant potency in binding to other tested gens and participation of cysteine SH-functional group in such interaction.

p300 Serine 89: A Critical Signaling Integrator and Its Effects on Intestinal Homeostasis and Repair

Differential usage of Kat3 coactivators, CBP and p300, by β-catenin is a fundamental regulatory mechanism in stem cell maintenance and initiation of differentiation and repair. Based upon our earlier pharmacologic studies, p300 serine 89 (S89) is critical for controlling differential coactivator usage by β-catenin via post-translational phosphorylation in stem/progenitor populations, and appears to be a target for a number of kinase cascades. To further investigate mechanisms of signal integration effected by this domain, we generated p300 S89A knock-in mice. We show that S89A mice are extremely sensitive to intestinal insult resulting in colitis, which is known to significantly increase the risk of developing colorectal cancer. We demonstrate cell intrinsic differences, and microbiome compositional differences and differential immune responses, in intestine of S89A versus wild type mice. Genomic and proteomic analyses reveal pathway differences, including lipid metabolism, oxidative stress response, mitochondrial function and oxidative phosphorylation. The diverse effects on fundamental processes including epithelial differentiation, metabolism, immune response and microbiome colonization, all brought about by a single amino acid modification S89A, highlights the critical role of this region in p300 as a signaling nexus and the rationale for conservation of this residue and surrounding region for hundreds of million years of vertebrate evolution.

Photocatalytic methods for amino acid modification

This tutorial review introduces photocatalysis for amino acid modification and summarises recent advances in the field.

The Role of Phytochelatin Synthase in Phytoremediation Agent: Structural Conservation of Phytochelatin (PC) Synthase to Maintain Its Activity as Heavy Metal Detoxification in Plant

Phytochelatin (PC) Enzyme has crucial role in heavy metal detoxification and homeostasis in plants. This study aimed to evaluate the genetic variation of PC synthase related to its activity based on structural comparison. We evaluated PC genes and protein sequences from 6 plants namely, Brassicasp., Amaranthussp., Noccaeasp., Arabidopsissp., Nicotianasp., and Pterissp. All sequences were aligned based on CLUSTALW matrix for DN sequences and MUSCLE algorithm for protein sequences. Data were clustered using MEGA Software for similarity clustering. Selected data were further modeled using SWISSMODEL to evaluate the 3D-structural analysis based on homology modeling. Thus, all protein models were superimposed and evaluated the structure comparison based on RMSD data. The result showed that genetic variation of PC gene is high among species. But it is clustered for the same species has similar sequence. In addition, protein sequences also showed the high diversity among species and it is still clustered basedon their genus. RMSD data showed that PC synthase from 6 plant has similar structure and tend to conserved even there is genetic variation or amino acid modification. We concluded that structural of PC gene is more conserved than its sequences. It is important to keep its function among species.

Bio- and medicinally compatible α-amino acid modification via merging photo-redox and N-heterocyclic carbene catalysis

An NHC and photo-redox co-catalyzed α-amino acid decarboxylative carbonylation reaction was presented here. This method displayed good scope generality, providing an easy and direct pathway to access various downstream α-amino ketones from readily accessible starting materials under bio- and medicinally compatible conditions. Moreover, this strategy is appealing to chemical biology since it has great potential for chemical modification of peptides or late-stage synthesis of keto-peptides.

Bio- and medicinally compatible α-amino acid modification via merging photo-redox and N-heterocyclic carbene catalysis

An NHC and photo-redox co-catalyzed α-amino acid decarboxylative carbonylation reaction was presented here. This method displayed good scope generality, providing an easy and direct pathway to access various downstream α-amino ketones from readily accessible starting materials under bio- and medicinally compatible conditions. Moreover, this strategy is appealing to chemical biology since it has great potential for chemical modification of peptides or late-stage synthesis of keto-peptides.

Challenges and Opportunities in Identifying and Characterising Keratinases for Value-Added Peptide Production

Keratins are important structural proteins produced by mammals, birds and reptiles. Keratins usually act as a protective barrier or a mechanical support. Millions of tonnes of keratin wastes and low value co-products are generated every year in the poultry, meat processing, leather and wool industries. Keratinases are proteases able to breakdown keratin providing a unique opportunity of hydrolysing keratin materials like mammalian hair, wool and feathers under mild conditions. These mild conditions ameliorate the problem of unwanted amino acid modification that usually occurs with thermochemical alternatives. Keratinase hydrolysis addresses the waste problem by producing valuable peptide mixes. Identifying keratinases is an inherent problem associated with the search for new enzymes due to the challenge of predicting protease substrate specificity. Here, we present a comprehensive review of twenty sequenced peptidases with keratinolytic activity from the serine protease and metalloprotease families. The review compares their biochemical activities and highlights the difficulties associated with the interpretation of these data. Potential applications of keratinases and keratin hydrolysates generated with these enzymes are also discussed. The review concludes with a critical discussion of the need for standardized assays and increased number of sequenced keratinases, which would allow a meaningful comparison of the biochemical traits, phylogeny and keratinase sequences. This deeper understanding would facilitate the search of the vast peptidase family sequence space for novel keratinases with industrial potential.