Zinc binding with l-dopa peptides

Veldkamp, Kelsey; Tubergen, Philip J.; Swartz, Mason A.; DeVries, Jodie T.; Tatko, Chad D.

doi:10.1016/j.ica.2017.02.006

Cited by 10 publications

(9 citation statements)

References 49 publications

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“…Since there is no histidine in these ZCPs, and indole group was concluded not to be the zinc binding site (Figure 4A), free carboxyls at the C-terminus were found to be the primary zinc binding sites. They are essential to chelate divalent metal ions to form stable peptide-zinc complexes [51,53].…”

Section: Resultsmentioning

confidence: 99%

Zinc-Chelating Mechanism of Sea Cucumber (Stichopus japonicus)-Derived Synthetic Peptides

et al. 2019

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In this study, three synthetic zinc-chelating peptides (ZCPs) derived from sea cucumber hydrolysates with limited or none of the common metal-chelating amino-acid residues were analyzed by flame atomic absorption spectroscopy, circular dichroism spectroscopy, size exclusion chromatography, zeta-potential, Fourier transform infrared spectroscopy, Raman spectroscopy and nuclear magnetic resonance spectroscopy. The amount of zinc bound to the ZCPs reached maximum values with ZCP:zinc at 1:1, and it was not further increased by additional zinc presence. The secondary structures of ZCPs were slightly altered, whereas no formation of multimers was observed. Furthermore, zinc increased the zeta-potential value by neutralizing the negatively charged residues. Only free carboxyl in C-terminus of ZCPs was identified as the primary binding site of zinc. These results provide the theoretical foundation to understand the mechanism of zinc chelation by peptides.

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Section: Resultsmentioning

confidence: 99%

Zinc-Chelating Mechanism of Sea Cucumber (Stichopus japonicus)-Derived Synthetic Peptides

et al. 2019

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“…The causes of zinc deficiency include insufficient zinc intake, inadequate absorption, increased demand, and increased excretion, which is attributed to continuous administration of chelating drugs; levodopa being a known drug having this effect. Drugs with ≥2 hydroxide ions, such as levodopa, may chelate zinc and stabilize it by forming a five-or six-membered ring [16]; these chelated compounds are in turn excreted in the urine, which may result in zinc deficiency. Previous studies of serum zinc concentration in drug chelates have already been investigated in rats.…”

Section: Discussionmentioning

confidence: 99%

Correlation between Serum Zinc Levels and Levodopa in Parkinson’s Disease

et al. 2021

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Long-term intake of potential zinc-chelating drugs may cause zinc deficiency. We postulated that zinc deficiency in Parkinson’s disease (PD) patients was related to the intake of drugs such as levodopa. We investigated the relationship between zinc levels and levodopa administration period, dosage, and symptoms of zinc deficiency in PD patients. We measured serum zinc levels and analyzed correlations between serum zinc levels, the levodopa oral administration period, dosage, dosing frequency, and zinc deficiency symptoms including taste disorders. Data analyses were performed using Spearman’s rank correlation coefficient. The mean serum zinc level was 60.5 ± 11.6 μg/dL. The mean administration period for levodopa was 8.0 ± 5.5 years, mean administration frequency 3.4 ± 0.9 times/d, and mean administration dose 420.6 ± 237.1 mg/d. Negative correlations between zinc levels and levodopa dosage and dosing frequency were found. Multiple regression analysis showed a significant correlation with the frequency of levodopa (β = −0.360, p = 0.007). No significant change in clinical symptoms was observed after zinc administration, but anxiety tended to improve. Our results indicated that frequent levodopa administration strongly influenced serum zinc levels which may have alleviating effects on psychiatric symptoms; therefore, preventing zinc deficiency can be important during PD treatment.

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“…Furthermore, it has been reported that some drugs possess zinc‐chelating capability and may be the reason for drug‐related taste diabetes mellitus disturbances (Tomita & Yoshikawa, ). It has been reported that L‐dopa may induce zinc deficiency (Tomita & Yoshikawa, ), which chelates zinc (Veldkamp, Tubergen, Swartz, DeVries, & Tatko, ). Prior to this study, no reports showed serum zinc levels decreasing progressively with LCIG treatment.…”

Section: Discussionmentioning

confidence: 99%

Proposition of zinc supplementation during levodopa–carbidopa intestinal gel treatment

et al. 2018

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ObjectivesLevodopa–carbidopa intestinal gel (LCIG) infusion is a useful therapy for the wearing‐off phenomenon of advanced Parkinson's disease (PD) patients. Recently, we found three PD patients that may have had a zinc deficiency after the LCIG infusion, possibly due to the zinc‐chelating action of levodopa. This study aims to evaluate changes in serum zinc levels in three patients that received LCIG treatment and to determine possible remedies for zinc deficiency during treatment.Materials and MethodsWe performed a prospective blood analysis of serum zinc levels before, when possible, and after LCIG treatment in our three PD patients.ResultsThe serum zinc levels of the first patient before treatment and 4 months after beginning LCIG treatment were 69 and 58 μg/dl, respectively. For the second patient, serum zinc levels before treatment and two months after starting LCIG treatment were 87 and 46 μg/dl, respectively. The baseline serum zinc level for the third patient was not examined, but was 48 μg/dl 5 months after starting the LCIG infusion.ConclusionsLevodopa–carbidopa intestinal gel infusion might have caused a zinc deficiency through levodopa zinc chelation. Zinc deficiency with LCIG infusion has not yet been reported, though preventing zinc deficiency may be an important factor in future LCIG treatment strategies.

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Zinc binding with l-dopa peptides

Cited by 10 publications

References 49 publications

Zinc-Chelating Mechanism of Sea Cucumber (Stichopus japonicus)-Derived Synthetic Peptides

Zinc-Chelating Mechanism of Sea Cucumber (Stichopus japonicus)-Derived Synthetic Peptides

Correlation between Serum Zinc Levels and Levodopa in Parkinson’s Disease

Proposition of zinc supplementation during levodopa–carbidopa intestinal gel treatment

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