L-Propargylglycine

Details:

Boiling point     272.1±35.0 °C(Predicted)
density     1.209±0.06 g/cm3(Predicted)
storage temp.     Inert atmosphere,2-8°C
pka    2.04±0.10(Predicted)
form     Powder
color     White to pale yellow
BRN     2347861
InChIKey    DGYHPLMPMRKMPD-BYPYZUCNSA-N
CAS DataBase Reference    23235-01-0(CAS DataBase Reference)
Safety Information
Safety Statements     22-24/25
WGK Germany     3
F     10
HS Code     29224999
MSDS Information
Provider    Language
SigmaAldrich    English
L-Propargylglycine Usage And Synthesis
Chemical Properties    White powder
Enzyme inhibitor    This alkynyl amino acid and mechanism-based inhibitor (FW = 113.11 g/mol; CAS 23235-01-0), also known as (S)-2-amino-4-pentynoic acid, irreversibly inactivates γ-cystathionase (an enzyme that also catalyzes the synthesis of the metabolic signaling gas, H2S, See also Hydrogen Sulfide), acting as a Michael addition type suicide inhibitor of cystathionine γ-lyase, cystathionine γ-synthase, alanine aminotransferase, and methionine γ-lyase. Propargylglycine inactivates γ-cystathionase with pseudo-first-order kinetics and incorporation of 1 mol inhibitor per 80 kDa enzyme. When studied in vivo, inactivation of cystathionine γ-lyase in rat kidney was less than that in the liver, owing to the presence of a higher cysteine concentration in kidney. L-Propargylglycine was found to inactivate pig heart L-alanine transaminase (EC 2.6.1.2) at 37o C with a Ki = 3.9 mM, an observed maximal first order rate constant, kinact = 0.26 min–1, a minimal stoichiometric ratio necessary for inactivation of 2.7 L-propargylglycine molecules/enzyme subunit, with 2.2 molecules/subunit undergoing transamination before inactivation ensues. Experimental cystathioninuria, induced in rats by administration of D,L-propargylglycine, results in the formation of the cystathionine metabolites, cystathionine ketimine and perhydro-1,4-thiazepine-3,5-dicarboxylic acid, in various regions of the brain. L-Propargylglycine irreversibly inactivates proline dehydrogenase, which catalyzes the first step of proline catabolism, oxidizing proline to pyrroline-5-carboxylate. The 1.9- resolution structure of the inactivated Thermus thermophilus enzyme shows that N5 of the flavin cofactor is covalently connected to the e-amino group of Lys-99 via a three-carbon linkage, consistent with the mass spectral analysis of the inactivated enzyme. The isoalloxazine ring has a butterfly angle of 25o, suggesting the cofactor is reduced. Two mechanisms, both involving oxidation to N-propargyliminoglycine, can account for these properties. L-Propargylglycine irreversibly inhibits L-amino acid oxidase from the venom of Crotalus adamanteus (Eastern diamondback rattlesnake) and Crotalus atrox (Western diamondback rattlesnake) in a dose- and timedependent manner that was blocked by the substrate L-phenylalanine. Other targets include methionineγ-lyase and UDP-Nacetylmuramate: L-alanine ligase, or L-alanine-adding enzyme, or UDP-Nacetylmuramoyl- L-alanine synthetase.
Purification Methods    The acid crystallises readily when ~4g in 50mL H2O are treated with absolute EtOH at 4o/3hours, and is collected, washed with cold absolute EtOH and Et2O and dried in a vacuum. Also, it recrystallises from aqueous Me2CO, RF on SiO2 TLC plates with n-BuOH/H2O/AcOH (4:1:1) is 0.26. The racemate has m 238-240o. [Leukart et al. Helv Chim Acta 59 2181 1976, Eberle & Zeller Helv Chim Acta 68 1880 1985, Jansen et al. Recl Trav Chim Pays-Bas 88 819 1969.] It is a suicide inhibitor of -cystathionase and other enzymes [Washtier & Abeles Biochemistry 16 2485 1977, Shinozuka et al. Eur J Biochem 124 377 1982].
L-Propargylglycine Preparation Products And Raw materials
Preparation Products    FMOC-L-PROPARGYLGLYCINE