D-Penicillamine N-acetyl

N-acetyl-L-cysteine and N-acetyl-D-penicillamine are the simplest ligands containing the thiolate and amide donor functions in the same molecule. For understanding the coordination chemistry of L-cysteine and its peptide derivatives, it is important to take into account that the thiol group can form a five-membered chelate with the amide-N and a six-membered one with the carboxylate-O donor atoms. All studies rule out a cadmium(ll)-induced amide coordination in these complexes, therefore the formation of the (S,0) chelate is the governing factor during complex formation with N-acetyl-L-cysteine. The equilibrium data have... 

For this method S-nitroso-N-acetyl-D, L-penicillamine (SNAP, FW = 220.3) is decomposed to NO in solution in the presence of a Cu (I) catalyst [77], The resultant NO generated can then be used to calibrate the sensor. The reaction proceeds in accordance to the following reaction ... 

Doornbos DA, Faber JS. Studies on metal complexes of drugs. D-penicillamine and N-acetyl-D-peniciUamine. Pharm Weekbl 1964 99 289-309. 

Doornbos DA. Stabihty constants of metal complexes of L-cysteine, D-penicillamine, N-acetyl-D-peniciUamine and some biguanides. Determination of stoichiometric stabihty constants by an accurate method for pH measurement. Pharm Weekbl 1968 103(45) 1213-27. 

Doombos DA and Faber J, Metal complexes of dmgs. d-penicillamine and N-acetyl-o-penicillamine, Pharm. Weekbl., 99, 289-309 (1964). 

Using chiral thiols for derivative formation, isoindoles are formed from amino acids and amino alcohols. BOC-L-cysteine, N-acetyl-L-cysteine, Af-acetyl-D-penicillamine [340] and l-thio-jS-D-glucose [341] have been shown to be suitable reagents which allow the separation of most amino acid enantiomers using reversed phase column chromatography. Thus, OPA/N-acetyl-L-cysteine has been used among others for the separation of enantiomers of aspartate [342], baclofen [343], norepinephrine, dopa [344] and lombricine [345]. 

Increased oxidative stress in the RAW 264.7 macrophage cell line is partially mediated via the S-nitrosothiol-induced inhibition of glutathione reductase (EC 1.6.4.2) (Butzer et al. 1999). Fujii et al. (2000) isolated a cDNA for rat glutathione reductase and constructed a baculovirus system to produce recombinant glutathione reductase on a large scale. NO donors (S-nitrosoglutathione, SIN-1, and S-nitroso-N-acetyl-D,L-penicillamine) inhibited the enzymatic activities of purified glutathione reductase. 

The nitric oxide donor, S-nitroso-N-acetyl-D,L-penicillamine induced dose-dependent inhibition of IL-1 production in LPS-stimulated rat alveolar macrophages in which endogenous nitric oxide production was blocked (Persoons et al. 1996). 

When cultured rat alveolar macrophages were stimulated with LPS, substantial amounts of nitric oxide were produced (Persoons et al. 1996). Inhibition of the nitric oxide production by the l-arginine analogue, N -monomethyl-L-arginine resulted in an increase of IL-ip and lL-6, whereas TNF-a concentrations remained unchanged. Conversely, the nitric oxide donor, S-nitroso-N-acetyl-D,L-penicillamine induced dose dependent inhibition of IL-1 production in LPS-stimulated alveolar macrophages in which endogenous nitric oxide production was blocked. 

Nitric oxide donors [sodium nitroprusside, S-nitroso-N-acetyl-D,L-penicillamine or l-hydroxy-2-oxo-3-(N-methyl-6-aminohexyl)-3-methyl-l-triazene = NOC-9] did not affect the activities of non-specific alkaline phosphatase and non-specific esterase in rat and mouse kidney proximal tubulo-cytes which do not contain nitric oxide synthase I (Dahrmann etal. 1997). However, the activities of succinate dehydrogenase (EC 1.3.99.1), cytochrome c oxidase (EC 1.9.3.1), catalase (EC 1.11.1.6), peroxidase (EC 1.11.1.7), and cholinesterase (EC 3.1.1.7) and different types of adenosine triphosphatase (EC 3.6.1.3) were found reduced. 

Clinical reports indicate that mercury excretion can be enhanced by the oral administration of A-acetyl-D,L-penicillamine (Kark et al. 1971), DMPS (Campbell et al. 1986 Hruby and Donner 1987), or DMSA (Roels et al. 1991 Fournier et al. 1988 Bluhm et al. 1992), but the disappearance of symptoms may be very slow or only partial. Since DMSA is superior to N-acetyl-D,L-penicillamine in animal experiments and is more readily available, it would appear to be the most useful compound for current clinical treatments. 

N-Acetyl-penicillamine [D- 15537-71-0, DL-59-53-0J M 191.3, m 183", 186-187" (DL-form), 189-190" (D-form), [a] +18" (c 1, 50% EtOH). Roth forms are recrystd from hot H2O. A pure sample of the D-foim was obtained after five recrystns. [Crooks in The Chemistry of Penicillin Clarke, Johnson and Robinson eds, Princeton University Press, 470 7949]. 

Kark RA, Poskanzer DC, Bullock JD, Boylen G (1971) Mercury poisoning and its treatment with A -acetyl-D,L-penicillamine. N Engl J Med 285 10-16 Kontoghiorghes GJ, Aldouri MA, Sheppard L, Hoffbrand AV (1987) 1,2-Dimethyl-3-hydroxypyrid-4-one, an orally active chelator for treatment of iron overload. Lancet 1 1294-1295... 

ZnHL2 24.43 (cysteine), 25.23 (D-penicillamine), 18.39 (N-acetyl-cysteine), 20.76 (cysteine-methylester). ZnH i L 2,71 (N-acetyl-cysteine), 0.41 (cysteine-methylester). 

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