L-Penicillamine

The identification of chiral penicillamine (Pen) is of great significance for clinical medication safety. The host-guest systems formed by enantiomers and macromolecule can be applied to differentiate the chiral drugs and enable the drug delayed release. We hereby performed the dispersion corrected density functional theory (DFT-D) calculation on the complex formed by β-cyclodextrin(β-CD) and D/L-penicillamine (D/L-Pen). The diverse encapsulation configurations with different interaction energy show that both D-Pen and L-Pen tend to longitudinally embedded into the narrow aperture of β-CD with the front part of the sulfur group and the methyl group, and the interaction energy between L-Pen and β-CD is 5.47 kJ/mol(M062XD3) lower than that between D-Pen and β-CD. Based on the computed vibration frequency of host, guest, and the most stable complex, it is found that the featured peaks attributed to the vibration of the carboxyl group of guest and the skeleton vibration of complex are the most significant spectral standard to distinguish the β-CD-D/L-Pen and β-CD. Moreover, the peaks resulted from the skeleton vibration in terahertz spectra can be also used to distinguish the complex of β-CD with chiral Pen. Through the topological analysis and the Independent Gradient Model (IGM) analysis, the O-H…O hydrogen bond in β-CD-D-Pen is stronger than that in β-CD-L-Pen, and the van der Waals interactions such as C-H…O,C-H…N,C-H…S, O…S and C-H…C-H have the most contributions to the intermolecular interaction in β-CD-D/L-Pen. It is also noted that the H(-OH) in D-Pen and S in L-Pen contribute the most to the intermolecular interaction with β-CD in comparison with other atoms in Pen.

N-Terminally free but C-terminally amidated peptides Pen-SSACS-NH2and CSSA-Pen-S-NH2containing l-penicillamine (Pen) in sequence have been synthesized and their nickel(ii), zinc(ii) and cadmium(ii) complexes were studied by potentiometric and spectroscopic measurements. This study is the first example of the synthesis and metal complexes of peptides containing penicillamine in a peptide sequence constructed from natural amino acids. The data were compared to those of the two cysteine counterparts, CSSACS-NH2. It was found that the replacement of l-cysteine with l-penicillamine has a significant impact on the complex formation processes with nickel(ii) ions. The major differences include the suppression of polynuclear complex formation, the enhanced metal binding affinity of the amino terminus and the increased tendency for the formation of amide bonded species. The tridentate (NH2,S-,S-) coordination was characteristic of the zinc(ii) and cadmium(ii) complexes in the case of all three peptides containing two thiolate functions.

Background:Pre-eclampsia (PE) complicates approximately 5-7% of all pregnancies. This study investigates the effects of S-nitroso-N-acetylpenicillamine (SNAP) and S-nitrosoglutathione (GSNO) on the classical features of PE.Materials and methods:On day 14 of gestation, female Sprague-Dawley rats were separated into five groups and treated intravenously for 7 days as follows: (i) 0.3 mL 0.9% saline (control, n = 11); (ii) 50 mg/kg Body Weight (BW) N-nitro-L-arginine methyl ester (L-NAME) in 0.3 mL saline (n = 10); (iii) 50 mg/kg BW L-NAME and 8 mg/kg BW GSNO in 0.15 mL saline (n = 6); (iv) 50 mg/kg BW L-NAME in 0.15 mL saline and 8 mg/kg BW SNAP in 0.15 mL DMSO (n = 9); and (v) 0.15 mL DMSO and 0.15 mL saline (SNAP control, n = 7). Blood pressures were measured on day 14 through day 20, a 4-h urine sample was taken on day 20, and animals were sacrificed on day 21. Pups were counted and weighed individually.Results:SNAP and GSNO significantly decreased systolic, diastolic, and mean arterial pressures in PE-induced rats from day 14 through day 20 (P < 0.05). Pup weights in SNAP and GSNO groups were higher than in L-NAME group but lower than in controls (P ≤ 0.001). SNAP and GSNO partially reversed growth retardation.Conclusion:Elevated blood pressure, proteinuria, and intrauterine growth restriction associated with PE were induced in Sprague-Dawley rats using L-NAME. These were partially reversed with the use of GSNO and SNAP. The mechanism of action of these S-nitrosothiols (RSNOs) should be further explored.