The human islet amyloid polypeptide (hIAPP) or amylin, a neuroendocrine peptide hormone, is known to misfold and form amyloidogenic aggregates that have been observed in the pancreas of 90% subjects with Type 2 Diabetes Mellitus (T2DM). Under normal physiological conditions, hIAPP is co-stored and co-secreted with insulin; however, under chronic hyperglycemic conditions associated with T2DM, the overexpression of hIAPP occurs has been associated with the formation of amyloid deposits; as well as the death and dysfunction of pancreatic β-islets in T2DM. Hitherto, various biophysical and structural studies have shown that during this process of aggregation, the peptide conformation changes from random structure to helix, then to β-sheet, subsequently to cross β-sheets, which finally form left-handed helical aggregates. The intermediates, formed during this process, have been shown to induce higher cytotoxicity in the β-cells by inducing cell membrane disruption, endoplasmic reticulum stress, mitochondrial dysfunction, oxidative stress, islet inflammation, and DNA damage. As a result, several research groups have attempted to target both hIAPP aggregation phenomenon and the destabilization of preformed fibrils as a therapeutic intervention for T2DM management. In this review, we have summarized structural aspects of various forms of hIAPP viz. monomer, oligomers, proto-filaments, and fibrils hIAPP. Subsequently, cellular toxicity caused by toxic conformations of hIAPP has been discussed. Finally, the need for performing structural and toxicity studies in vivo to fill in the gap between the structural and cellular aspects has been discussed.

Unambiguous identification and precise quantification of enantiomers in chiral mixtures is crucial for enantiomer specific synthesis as well as chemical analysis. The task is often challenging for mixtures with high enantiomeric excess and for complex molecules with strong (1)H-(1)H scalar (J) coupling network. The recent advancements in (1)H-(1)H decoupling strategies to suppress the J-interactions offered new possibilities for NMR based unambiguous discrimination and quantification enantiomers. Herein, we discuss a high resolution two-dimensional pure-shift zCOSY NMR method with homonuclear band-selective decoupling in both the F1 and F2 dimensions (F1F2-HOBS-zCOSY). This advanced method shows a sharp improvement in resolution over the other COSY methods and also eliminates the problems associated with the overlapping decoupling sidebands. The efficacy of this method has been exploited for precise quantification of enantiomeric excess (ee) ratio (R/S) up to 99:1 in the presence of very low concentrations of chiral lanthanide shift reagents (CLSR) or chiral solvating agents (CSA). The F1F2-HOBS-zCOSY is simple and can be easily implemented on any modern NMR spectrometers, as a routine analytical tool.

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The present manuscript focuses on fast and simultaneous determination of H- H and H- F scalar couplings in fluorinated complex steroid molecules. Incorporation of broadband PSYCHE homonuclear decoupling in the indirect dimension of zero-quantum filtered diagonal experiments (F1-PSYCHE-DIAG) suppresses H- H scalar couplings; however, it retains H- F scalar couplings (along F1 dimension) for the F coupled protons while preserving the pure-shift nature for H resonances uncoupled to F. In such cases, along the direct dimensions, H- H scalar coupling multiplets deconvolute and they appear as duplicated multiplets for the F coupled protons, which facilitates unambiguous discrimination of F coupled H chemical sites from the others. Further, as an added advantage, data acquisition has been accelerated by invoking the known ideas of spectral aliasing in the F1-PSYCHE-DIAG scheme and experiments demand only ~10 min of spectrometer times.

At the present time, when NMR spectrometers are getting prohibitively expensive, for routine applications in chemistry where NMR is an indispensable technique, working with tabletop low field spectrometers would be an attractive proposition. However, as is well known, chemical shift dispersion is a serious limitation on these systems. The modern strategies of pure shift spectroscopy would not be useful because of lack of gradients, on the one hand, and even when they are there, there will be an extreme loss of sensitivity by slice selective gradients in the pulse sequences, on the other. The present manuscript presents an approach for resolution enhancement by employing processing-based advancements in the pure shift NMR schemes and presents data acquired on a 60 MHz NMR spectrometer. We use generalized indirect covariance (GIC) processing based reconstruction for enhancing the resolution in 2D-NMR spectra and that has been demonstrated on different small organic molecule samples.Development of analytical methods for structural chemistry is very important in understanding the modications that have taken place during chemical reactions. In this respect, spectroscopic techniques have been well recognized to obtain accurate information on analytes (either it could be a pure molecule or mixture of small molecules). Amongst them, NMR has been proven to provide the atomic level structural information of chemical constituents present in the reaction processes.1 The advent of high-eld super conducting magnets with cryo-probe technologies has made the chemical structural analysis simple. Laterally, the development of cryogenic free permanent eld homogeneous tabletop magnets has made a signicant impact as this is cost effective, a lot less maintenance and does not require great NMR expertise to operate them. Indeed, several analytical applications of tabletop NMR systems have been reported (edible oils, 2 fats, 3 quality control of pharmaceutical drugs, 4 food, 5 mobile sensor-MRI 6 and reaction monitoring 7-10 ). Further, because of the low costs, these instruments have found a common place in undergraduate educational laboratories.It is well known that 2D-NMR experiments signicantly enhance spectral resolution and facilitate unambiguous analysis. However, at low magnetic elds, severely overlapped scalar coupling multiplets belonging to different chemical sites hamper the chemical shi resolution, even in 2D-NMR spectra and this need to be sorted out to be able to identify the molecules present in a reaction mixture. In this sense, pure shi NMR methods help to enhance the resolution by obtaining exclusively chemical shi information (couplings are removed) in the spectra.11 On the other hand, the various sophisticated pure shi NMR methods such as, versions of Zangger-Sterk, 12 BIRD, 13 HOBS, 14and PSYCHE 15 broadband decoupling methods, that have been developed on modern high eld spectrometers, are difficult to implement on low eld spectrometers and are currently not available.The present manuscript offers a so...

Application of NUS along with BEST NMR experiments has been demonstrated for obtaining the important residue-specific atomic level backbone chemical shift values in short durations of time.

Some novel chemically modified frameworks of ursolic acid have been designed and synthesized. The key step was the cycloaddition of azidopropyl-3β-hydroxy-urs-12-en-28-oate with the appropriate C28 propargyl esters of ursolic, corosolic, asiatic, oleanolic, and betulinic acid under Click reaction conditions, and the products were obtained in 74-84% yields. In view of their intriguing structural diversity, they have been subjected to detailed 1D and 2D NMR studies and their structures are thoroughly assigned. The synthesized compounds were screened for their anticancer potential against two human breast cancer cell lines (MCF-7 & MDA-MB-231) using sulforhodamine B cell proliferation assay. The GI data revealed that the synthesized compounds exhibit highly potent activities against the two tested cell lines. Interestingly, the synthesized compounds showed selectivity and higher activity against MDA-MB-231 cell line than MCF-7. Among the tested compounds, compound 17 is the most potent one with GI value of 1.4 ± 0.1 μM and showed 2.9 times more activity than the standard doxorubicin against MDA-MB-231. In addition, 17 arrests cells in mitotic phase of cell cycle, resulting in a change in cell phenotype. In view of the selective and highly promising activity against breast cancer cell lines, these compounds can serve as promising leads for further development.