PubMed · 12357190
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Ross W Appleyard. 2002. Old lessons forgotten.. https://doi.org/10.1097/00000542-200210000-00062
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The interaction of extracellular matrix with cells regulates their adhesion, migration and proliferation, and it is believed that damage to vascular matrix components is a factor in the development of atherosclerosis. Evidence has been provided for a role for the haem enzyme MPO (myeloperoxidase), released by activated monocytes (and possibly macrophages), in oxidative events within the artery wall. As MPO is released extracellularly, and is highly basic, it might be expected to associate with poly-anionic matrix components thereby localizing damage to these materials. In this study the reaction of the MPO-derived oxidant hypochlorous acid (HOCl) with extracellular matrix from vascular smooth muscle cells and healthy pig arteries has been examined. HOCl is rapidly consumed by such matrix samples, with the formation of matrix-derived chloramines or chloramides. The yield of these intermediates increases with HOCl dose. These materials undergo a time- and temperature-dependent decay, which parallels the release of sugar and protein components from the treated matrix, consistent with these species being important intermediates. Matrix damage is enhanced by species that increase chloramine/chloramide decomposition, with copper and iron ions being effective catalysts, and decreased by compounds which scavenge chloramines/chloramides, or species derived from them. The effect of such matrix modifications on cellular behaviour is poorly understood, though it is known that changes in matrix materials can have profound effects on cell adhesion, proliferation, growth and phenotype. The observed matrix modifications reported here may therefore modulate cellular behaviour in diseases such as atherosclerosis where MPO-derived oxidants are generated.
Interactions between N-methylacetamide (NMA) and N-methylated derivatives of uracil, isocyanurate and barbituric acid have been studied using ab initio methods at the local MP2/6-31G** level of theory. The results were compared to similar interactions between the oxygen atom of NMA and the pi-clouds of perfluorobenzene, quinone and trimethyltriazine. The pi-acidic amides of isocyanurate and barbituric acid were found to interact with a hydrogen bond acceptor primarily through electrostatic attractions. These groups may be used as alternatives of a hydrogen bond donor to complement a hydrogen bond acceptor or an anion in molecular recognition and drug design. Examples of such interactions were identified through a search of the CSD database.
The asymmetric synthesis of novel, potent phosphoramidate alpha(2-6)sialyltransferase transition-state analogue inhibitors such as (R)-9 (K(i)=68 microM) is described, via condensation of cytidine phosphitamide 6 with key chiral, non-racemic alpha-aminophosphonates, prepared in >98% ee by Mitsunobu azidation followed by Staudinger reduction of the corresponding chiral, non-racemic alpha-hydroxyphosphonates.