7 x 10(9) rotamers. This dynamic library has 74% overlap of rotamer distributions with rotamer libraries derived from static high-resolution crystal structures. Seventy-five percent of the residues had an assignable primary conformation, and 68% of the residues had at least one significant alternate conformation. The average correlation time for switching between rotamers ranged from 22 ps for Met to

over 8 ns for Cys; this time decreased 20-fold on the surface of the protein and modestly for dihedral angles further from the main chain. Side chain S(2) axis order parameters were calculated and they correlated well with those derived from NMR relaxation experiments (R = 0.9). Relationships relating the S(2) axis order parameters to rotamer occupancy were derived. Overall the Dynameomics rotamer library offers a comprehensive depiction of side chain rotamer preferences and dynamics in solution, and more realistic distributions Ilomastat research buy for dynamic proteins in solution at ambient temperature than libraries derived from crystal structures, in particular charged surface residues are better represented. Details of the rotamer library are presented here and the library itself can be downloaded at http://www.dynameomics.org.”
“Kynurenic acid (KYNA), a neuroactive metabolite of tryptophan that acts

on different receptors (e.g. those of N-methyl-D-aspartate (NMDA) and presynaptic alpha 7 nicotinic acetylcholine (nACh)), exerts fundamentally antiglutamatergic effects. In view of its antiglutamatergic properties, an elevation of the KYNA level within the brain might result in neuroprotection. However, the use of KYNA as a neuroprotective agent is rather PF-4708671 limited, because it crosses the blood brain barrier (BBB) to only a poor extent. During recent years, new KYNA derivatives have been developed which can readily traverse the BBB and also exert neuroprotection. However, as KYNA and its derivatives are able to interfere with glutamatergic and cholinergic transmission, the potential risks of interfering

with cognitive functions cannot be excluded. This in vivo study on anesthetized rats therefore tested the effects of the administration of KYNA and a KYNA derivative (SZR72) selleck chemicals (in a dosage that exerted neuroprotection) on long-term potentiation (LTP) and pure field excitatory postsynaptic potentials induced by contralateral CA3 region stimulation and recorded in the pyramidal layer of the CA1 region of the hippocampus. Surprisingly, KYNA and this derivative did not reduce, but rather increased the induceability of LTP. The possible explanation is discussed in detail. In brief: an elevated KYNA level in the perisynaptic area produced, for example, by exogenous prodrug or derivative administration exerts preferential effects on the extrasynaptic NMDA receptors and the nACh receptors on presynaptic glutamatergic terminals, while sparing the currents mediated by synaptic NMDA and alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptors.