Graph theoretical descriptors differentiate d-Mannose isomers in the principal component proposed feature space: A computational approach.

The intricate nature of carbohydrates, particularly monosaccharides, stems from the existence of several chiral centers within their tertiary structures. Predicting and characterizing the molecular geometries and electrostatic landscapes of these substances is difficult due to their complex electrical properties. Moreover, these structures can display a substantial degree of conformational flexibility due to the presence of many rotatable bonds. Moreover, identifying and distinguishing between D and L enantiomers of monosaccharides presents a significant analytical obstacle since there is a need for empirically measurable properties that can distinguish them. This work uses Principal Component Analysis (PCA) to explore the chemical information included in 3D descriptors in order to comprehend the conformational space of d-Mannose stereoisomers. The isomers may be discriminated by utilizing 3D matrix-based indices, geometrical descriptors, and RDF descriptors. The isomers can be distinguished by descriptors, such as the Harary-like index from the reciprocal squared geometrical matrix (H_RG), Harary-like index from Coulomb matrix (H_Coulomb), Wiener-like index from Coulomb matrix (Wi_Coulomb), Wiener-like index from geometrical matrix (Wi_G), Graph energy from Coulomb matrix (SpAbs_Coulomb), Spectral absolute deviation from Coulomb matrix (SpAD_Coulomb), and Spectral positive sum from Coulomb matrix (SpPos_Coulomb). Among these descriptors, the first two, H_RG and H_Coulomb, perform the best in differentiation among the 3D-Matrix-Based Descriptors (3D-MBD) class. The results obtained from this study provide a significant chemical insight into the structural characteristics of the compounds inside the graph theoretical framework. These findings are likely to serve as the basis for developing new methods for analytical experiments.

Mannose: a potential saccharide candidate in disease management.

There are a plethora of antibiotic resistance cases and humans are marching towards another big survival test of evolution along with drastic climate change and infectious diseases. Ever since the first antibiotic [penicillin], and the myriad of vaccines, we were privileged to escape many infectious disease threats. The survival technique of pathogens seems rapidly changing and sometimes mimicking our own systems in such a perfect manner that we are left unarmed against them. Apart from searching for natural alternatives, repurposing existing drugs more effectively is becoming a familiar approach to new therapeutic opportunities. The ingenious use of revolutionary artificial intelligence-enabled drug discovery techniques is coping with the speed of such alterations. D-Mannose is a great hope as a nutraceutical in drug discovery, against CDG, diabetes, obesity, lung disease, and autoimmune diseases and recent findings of anti-tumor activity make it interesting along with its role in drug delivery enhancing techniques. A very unique work done in the present investigation is the collection of data from the ChEMBL database and presenting the targetable proteins on pathogens as well as on humans. It shows Mannose has 50 targets and the majority of them are on human beings. The structure and conformation of certain monosaccharides have a decisive role in receptor pathogen interactions and here we attempt to review the multifaceted roles of Mannose sugar, its targets associated with different diseases, as a natural molecule having many success stories as a drug and future hope for disease management.

Polyphenol oxidase (PPO) arm of catecholamine pathway catalyzes the conversion of L-tyrosine to L-DOPA in Mucuna pruriens (L.) DC var. pruriens: An integrated pathway analysis using field grown and in vitro callus cultures.

Mucuna pruriens (L.) DC var. pruriens is the natural source for L-DOPA, precursor of the neurotransmitter dopamine, used widely in the treatment of Parkinson's disease. However, L-DOPA synthesis in plants is mediated either by Catecholamine (CA) pathway or alternate pathway catalyzed by Cytochrome P450 (CYP450) class of enzymes. Interestingly, the CA pathway itself can be initiated either by tyrosine hydroxylase (TH) or polyphenol oxidase (PPO). The CA pathway mediated synthesis of L-DOPA has not yet been proved in M. pruriens albeit strong indications. Therefore, the present investigation is focused on metabolite analysis of major intermediates of CA pathway up to the formation of dopamine and expression analysis of the selected genes, in different tissues and callus cultures. The four major intermediates, L-tyrosine, tyramine, L-DOPA and dopamine, were detected using NMR spectroscopy and quantified by HPLC in the callus cultures and in different tissues of the field plant, respectively. The various stages of leaf tissue were also analyzed for metabolite profiling. The relative amount of intermediates detected during the ontogeny of leaf indicates that PPO mediated conversion of L-tyrosine to dopamine through L-DOPA is relatively higher compared to dopamine production from tyramine. Among the two possible enzymes, activity of PPO was 6.5-fold more than TH in metabolically active young leaves compared to intermediate leaves. The gene expression profiles comprising upstream genes of L-tyrosine synthesis and downstream up to dopamine synthesis shows strong correlation with L-DOPA synthesis. The study validates CA pathway mediated synthesis of L-DOPA with PPO as candidate enzyme, in M. pruriens.