β-Alanine methyl ester hydrochloride

beta-Benzamido-alpha-(3-pyridyl)-DL-alpha-alanine hydrochloride was synthesized from 3-pyridinecarboxyaldehyde via the azlactone which was hydrolyzed to the acrylic acid before hydrogenation. The methyl ester was effectively resolved with subtilisin. The optical purity of the D-isomer was established, since the D-isomer was used in synthesis of antagonists of the luteinizing hormone releasing hormone.

The X-ray single-crystal structure of methyl 2-aminoisobutyrate hydrochloride (Me-AIB), a non-standard amino acid, is reported at 10, 30, 50, 70 and 100 K. Fourier maps indicate the presence of rotational disorder of the hydrogen atoms of the ester methyl group. To study this effect in detail, high resolution data were collected with synchrotron radiation. The non-spherical molecular electron density was predicted with invariom scattering factors and subtracted from the density obtained from a full multipole refinement. This allows disorder to be distinguished from the molecular electron density at each temperature. The disorder is reduced between 100 K and 30 K, but still detectable even at 10 K. Hence, difference densities can be applied for the purpose of electronic structure validation and have the advantage of an absence of noise over Fourier methods. Ultra-low temperature experiments are foreseen to be useful in reducing such kinds of disorder in ultra-high resolution protein crystallography.

The vasodilator nitric oxide (NO) is involved in the regulation of systemic blood pressure and local organ blood flow. Inhibitors of the constitutively expressed nitric oxide synthase in endothelial cells (eNOS), e.g., Nomega-nitro-L-arginine methyl ester hydrochloride (L-NAME), aggravated liver injury in a variety of models. On the other hand, inhibitors of the inducible NOS (iNOS), e.g., 2-aminoethyl-isothiourea (AET), were found to be beneficial during endotoxemia. The aim of this investigation was to study the effect of AET compared with L-NAME on liver microvascular blood flow and injury in more complex models with multiple insults, i.e., ischemia (20 min)-reperfusion (8 h) in combination with .5 mg/kg endotoxin (IRE). Male Fisher rats were treated with 10 mg/kg AET or L-NAME and subjected to IRE. At 8 h, liver injury (plasma ALT: 1320+/-164 U/L) was significantly increased in AET-treated (5,018+/-1,379 U/L) and L-NAME-treated groups (2,429+/-228 U/L).

Neurolathyrism is a motor neuron (MN) disease caused by β-N-oxalyl-L-α,β-diaminopropionic acid (L-β-ODAP), an AMPA receptor agonist. L-β-ODAP caused a prolonged rise of intracellular Ca(2+) ([Ca(2+)]i) in rat spinal cord MNs, and the [Ca(2+)]i accumulation was inversely proportional to the MN's life span. The [Ca(2+)]i rise induced by L-β-ODAP or (S)-AMPA was antagonized completely by NBQX, an AMPA-receptor blocker. However, blocking the L-type Ca(2+) channel with nifedipine significantly lowered [Ca(2+)]i induced by (S)-AMPA, but not that by L-β-ODAP. Tetrodotoxin completely extinguished the [Ca(2+)]i rise induced by (S)-AMPA or kainic acid, whereas that induced by L-β-ODAP was only attenuated by 65.6±6% indicating the prominent involvement of voltage-independent Ca(2+) entry. The tetrodotoxin-resistant [Ca(2+)]i induced by L-β-ODAP was blocked by 2-APB, Gd(3+), La(3+), 1-(β-[3-(4-methoxy-phenyl)propoxy]-4-methoxyphenethyl)-1H-imidazole hydrochloride (SKF-96365) and flufenamic acid, which all are blockers of the transient receptor potential (TRP) channels.