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Atsushi Kato, Zhao-Lan Zhang, Hong-Yao Wang, Yue-Mei Jia, Chu-Yi Yu, Kyoko Kinami, Yuki Hirokami, Yutaro Tsuji, Isao Adachi, Robert J Nash, George W J Fleet, Jun Koseki, Izumi Nakagome, Shuichi Hirono
This paper identifies the required configuration and orientation of α-glucosidase inhibitors, miglitol, α-1-C-butyl-DNJ, and α-1-C-butyl-LAB for binding to ntSI (isomaltase). Molecular dynamics (MD) calculations suggested that the flexibility around the keyhole of ntSI is lower than that of ctSI (sucrase). Furthermore, a molecular-docking study revealed that a specific binding orientation with a CH-π interaction (Trp370 and Phe648) is a requirement for achieving a strong affinity with ntSI. On the basis of these results, a new class of nortropane-type iminosugars, labystegines, hybrid iminosugars of LAB and calystegine, have been designed and synthesized efficiently from sugar-derived cyclic nitrones with intramolecular 1,3-dipolar cycloaddition or samarium iodide catalyzed reductive coupling reaction as the key step...
May 1, 2015: Journal of Organic Chemistry
Sankar Mohan, Razieh Eskandari, B Mario Pinto
In humans, four different enzymes mediate the digestion of ingested carbohydrates. First salivary and pancreatic α-amylases, the two endoacting retaining glucosidases, break down the complex starch molecules into smaller linear maltose-oligomers (LM) and branched α-limit dextrins (αLDx). Then two retaining exoglucosidases, maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI), convert those molecules into glucose in the small intestine. The small intestinal brush-border epithelial cells anchor MGAM and SI, and each contains a catalytic N- and C-terminal subunit, ntMGAM, ctMGAM, ntSI, and ctSI, respectively...
January 21, 2014: Accounts of Chemical Research
Bidraha Bagh, Gabriele Schatte, Jennifer C Green, Jens Müller
The aluminum and gallium dichlorides (Mamx)ECl(2)1a (E = Al; 82%) and 1b (E = Ga; 79%) (Mamx = 2,4-di-tert-butyl-6-[(dimethylamino)methyl]phenyl) reacted with dilithioferrocene or dilithioruthenocene to give [1]ferrocenophanes (2a, 2b) and [1]ruthenocenophanes (3a, 3b), respectively. The galla[1]ruthenocenophane 3b could be isolated from the reaction mixture through precipitation into hexane (50%), while 2a, 2b, and 3a underwent ring-opening polymerization under the reaction conditions of their formation reactions to give metallopolymers (M(w) (DLS) between 8...
May 9, 2012: Journal of the American Chemical Society
Lyann Sim, Carly Willemsma, Sankar Mohan, Hassan Y Naim, B Mario Pinto, David R Rose
Human maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI) are small intestinal enzymes that work concurrently to hydrolyze the mixture of linear alpha-1,4- and branched alpha-1,6-oligosaccharide substrates that typically make up terminal starch digestion products. MGAM and SI are each composed of duplicated catalytic domains, N- and C-terminal, which display overlapping substrate specificities. The N-terminal catalytic domain of human MGAM (ntMGAM) has a preference for short linear alpha-1,4-oligosaccharides, whereas N-terminal SI (ntSI) has a broader specificity for both alpha-1,4- and alpha-1,6-oligosaccharides...
June 4, 2010: Journal of Biological Chemistry
D Endeman, M Kamermans
Visual information in natural scenes is distributed over a broad range of intensities and contrasts. This distribution has to be compressed in the retina to match the dynamic range of retinal neurons. In this study we examined how cones perform this compression and investigated which physiological processes contribute to this operation. M- and L-cones of the goldfish were stimulated with a natural time series of intensities (NTSI) and their responses were recorded. The NTSI displays an intensity distribution which is skewed towards the lower intensities and has a long tail into the high intensity region...
February 1, 2010: Journal of Physiology
C M Alexander
OBJECTIVE: Reflexes of shoulder girdle muscles such as trapezius are evoked from muscle afferents supplying the forearm and hand in healthy subjects. These reflexes are thought to aid the stability of the shoulder during use of the arm and hand [Alexander CM, Harrison PJ. Reflex connections from forearm and hand afferents to shoulder girdle muscles in humans. Exp Brain Res 2003;148: 277-282.]. With this in mind, the objective of this investigation was to examine this trapezius reflex in subjects with non-traumatic shoulder instability (NTSI)...
December 2007: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
Moyed M Miften, Shiva K Das, Min Su, Lawrence B Marks
External beam radiotherapy is commonly used for patients with cancer. While tumor shrinkage and palliation are frequently achieved, local control and cure remain elusive for many cancers. With regard to local control, the fundamental problem is that radiotherapy-induced normal tissue injury limits the dose that can be delivered to the tumor. While intensity-modulated radiation therapy (IMRT) allows for the delivery of higher tumor doses and the sparing of proximal critical structures, multiple competing plans can be generated based on dosimetric and/or biological constraints that need to be considered/compared...
2004: Journal of Applied Clinical Medical Physics
M J Glass, J Huang, S A Aicher, T A Milner, V M Pickel
alpha-2A-adrenergic receptor (alpha2A-AR) agonists modulate diverse autonomic functions. These actions are believed to involve functionally specialized, second-order neurons in catecholamine-containing portions of the medial nucleus tractus solitarius (mNTS) at both intermediate (NTSi) and caudal (NTSc) levels. However, the cellular mechanisms subserving alpha2A-AR-mediated actions within the mNTS have yet to be established. Immunocytochemistry was employed to examine the subcellular distribution of alpha2A-AR in both the intermediate and caudal mNTS and its association with cells containing the catecholamine-synthesizing enzyme tyrosine hydroxylase (TH)...
April 30, 2001: Journal of Comparative Neurology
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