02740nas a2200181   4500008004100000022001400041245012200055210006900177260000900246300001600255490000600271520207900277100002202356700002702378700001902405700000502424856012902429       2021                        eng d  a2470-134300aAccurate identification of bioactive meliaceae limonoids by UHPLC-MS/ms based structure-fragment relationships (SFRs)0 aAccurate identification of bioactive meliaceae limonoids by UHPL  cOCT   a26454-264760 v63 aY Limonoids are bioactive plant specialized metabolites found in the Meliaceae family. The basic limonoids, i.e., azadiradione, epoxyazadiradione, and gedunin have been exploited for various bioactivities and therefore are the potential drug leads for tomorrow. However, their low abundance, structural similarity, and lack of adequate mass fragmentation data have hampered their accurate identification and quantification from various sources. In the present study, basic limonoids such as azadirone, azadiradione, epoxyazadiradione, and gedunin isolated from Neem were utilized for the synthesis of their derivatives and isotopologs. A total of 30 one compounds were used in this study among which five were isolated, two were biotransformed, and 24 were synthesized. Among the synthesized compounds nine are novel compounds including six deuterated analogs/isotopologs which are (1,3-H-2)-1,2dihydro-3 beta-hydroxyazadiradione (9), (1,3,16-H-2)-1,2-dihydro-3 beta-16 beta-dihydroxyazadiradione (10), 3 beta-hydroxyazadiradione (11), 3 beta-16 beta-dihydroxyazadiradione (12), (3-H-2)-3 beta-hydroxyazadiradione (13), (3,16-H-2)-3 beta-16 beta-dihydroxyazadiradione (14), (1,3,7-H-2)-1,2-dihydro-3 beta-hydroxy-7-deacetylazadiradione (15), 1,2,20,21,22,23-hexahydroazadiradione (17), and (1,3-H-2)-1,2-dihydro-3 beta-hydroxygedunin (29). These limonoids along with their semisynthesized derivatives were subjected to ultra high performance liquid chromatography mass spectrometry (UHPLC-MS/MS) and the fragmentation pathway was established based on structure-fragment relationships (SFRs), utilizing high resolution MS/MS data. We have developed a most reliable and easily reproducible protocol describing in depth analysis of SFRs based on the structural modifications and synthesis of isotopologs. Also, the MS/MS fragment library of these basic limonoids generated in this study acts as a fingerprint for accurate identification and quantification of limonoids by MS/MS analysis in various plant tissue extracts, phytopharmaceutical formulations and biological samples.1 aMulani, Fayaj, A.1 aNandikol, Sharvani, S.1 aHaldar, Saikat1 a  uhttps://library.ncl.res.in/content/accurate-identification-bioactive-meliaceae-limonoids-uhplc-msms-based-structure-fragment02242nas a2200241   4500008004100000022001400041245013700055210006900192260000900261300001200270490000800282520138800290653002301678653002401701653002801725653003401753653002601787100001701813700000501830700002001835700002001855856012501875       2021                        eng d  a0006-291X00aDynamic coupling analysis on plant sesquiterpene synthases provides leads for the identification of product specificity determinants0 aDynamic coupling analysis on plant sesquiterpene synthases provi  cJAN   a107-1140 v5363 a<p>Sesquiterpene synthases catalyse cyclisation of farnesyl pyrophosphate to produce diverse sesquiterpenes. Despite utilising the same substrate and exhibiting significant sequence and structural homology, these enzymes form different products. Previous efforts were based on identifying the effect of divergent residues present at the catalytic binding pocket on the product specificity of these enzymes. However, the rationales deduced for the product specificity from these studies were not generic enough to be applicable to other phylogenetically distant members of this family. To address this problem, we have developed a novel approach combining sequence, structural and dynamical information of plant sesquiterpene synthases (SSQs) to predict product modulating residues (PMRs). We tested this approach on the SSQs with known PMRs and also on sesquisabinene synthase 1 (SaSQS1), a SSQ from Indian sandalwood. Our results show that the dynamical sectors of SSQs obtained from molecular dynamics simulation and their hydrophobicity and vicinity indices together provide leads for the identification of PMRs. The efficacy of the technique was tested on SaSQS1 using mutagenesis. To the best of our knowledge, this is a first technique of this kind which provides cues on PMRs of SSQs, with divergent phylogenetic relationship. (C) 2020 Elsevier Inc. All rights reserved.</p>
10amolecular dynamics10aProduct specificity10aSesquiterpene synthases10aStatistical coupling analysis10aX-ray crystallography1 aSingh, Sneha1 a1 aSengupta, Durba1 aKulkarni, Kiran  uhttps://library.ncl.res.in/content/dynamic-coupling-analysis-plant-sesquiterpene-synthases-provides-leads-identification01476nas a2200229   4500008004100000022001400041245010200055210006900157260000900226300001400235490000700249520067700256100001900933700003100952700003000983700001901013700002701032700000501059700002701064700002501091856013001116       2021                        eng d  a1359-734500aSynthetic heparan sulfate ligands for vascular endothelial growth factor to modulate angiogenesis0 aSynthetic heparan sulfate ligands for vascular endothelial growt  cAPR   a3516-35190 v573 a<p>We report the discovery of a potential heparan sulfate (HS) ligand to target several growth factors using 13 unique HS tetrasaccharide ligands. By employing an HS microarray and SPR, we deciphered the crucial structure-binding relationship of these glycans with the growth factors BMP2, VEGF(165), HB-EGF, and FGF2. Notably, GlcNHAc(6-O-SO3-)-IdoA(2-O-SO3-) (HT-2,6S-NAc) tetrasaccharide showed strong binding with the VEGF(165) growth factor. In vitro vascular endothelial cell proliferation, migration and angiogenesis was inhibited in the presence of VEGF(165) and HT-2,6S-NAc or HT-6S-NAc, revealing the potential therapeutic role of these synthetic HS ligands.</p>1 aJain, Prashant1 aShanthamurthy, Chethan, D.1 aBen-Arye, Shani, Leviatan1 aYehuda, Sharon1 aNandikol, Sharvani, S.1 a1 aPadler-Karavani, Vered1 aKikkeri, Raghavendra  uhttps://library.ncl.res.in/content/synthetic-heparan-sulfate-ligands-vascular-endothelial-growth-factor-modulate-angiogenesis