Inhibition of human prion neuropeptide PrP106-126 aggregation by hexacoordinated ruthenium complexes

Wang, Xuesong; Zhang, Bingbing; Zhao, Cong; Wang, Yanli; He, Lei; Cui, Menghan; Zhu, Xiaotong; Du, Weihong

doi:10.1016/j.jinorgbio.2013.07.009

Cited by 19 publications

(12 citation statements)

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“…33 In our preliminary study, the binding modes of NAMI-A to PrP106-126 differ from that of the other hexa-coordinated ruthenium complexes. 27 The outer cationic group was also not detected in the adducts. The probable binding modes and the inhibitory effect of these ruthenium complexes on the peptide were further discussed.…”

Section: Discussionmentioning

confidence: 96%

“…[38][39][40][41] Among all ruthenium complexes, NAMI-A exhibits selective effects for solid tumor metastases and provides novel perspectives on cancer chemotherapy. 27 Given the efficient pharmaceutical activity and low cytotoxicity of NAMI-A, the present study tested three ruthenium complexes (KP418, KP1019, and KP1019-2) with configurations comparable with NAMI-A in terms of binding to PrP106-126. 27 Given the efficient pharmaceutical activity and low cytotoxicity of NAMI-A, the present study tested three ruthenium complexes (KP418, KP1019, and KP1019-2) with configurations comparable with NAMI-A in terms of binding to PrP106-126.…”

Section: Discussionmentioning

confidence: 99%

“…2. 27 The peak at 2389.89 (m/z = 1+) occurred after the addition of KP1019 into PrP106-126 and referred to the adduct of [PrP106-126 + RuCl 4 (Ind) 2 ] (Fig. The spectra varied after ruthenium complexes were incubated with PrP106-126.…”

Section: Nami-a-like Ruthenium Complexes Bind To Prp106-126mentioning

confidence: 99%

“…22 Recent studies used different metal complexes with various metal centers and chelating ligands against amyloid disorders. [25][26][27][28][29][30][31][32] Ruthenium complexes are considered potential inhibitors because of their low cytotoxicity and disaggregating ability. [25][26][27][28][29][30][31][32] Ruthenium complexes are considered potential inhibitors because of their low cytotoxicity and disaggregating ability.…”

Section: Introductionmentioning

confidence: 99%

“…42,43 Ruthenium polypyridyl complexes exhibit high potency in inhibiting AChE and disaggregating the Ab peptide. 27 The present work aims to explore the binding properties and inhibitory effects of NAMI-A-like ruthenium complexes on PrP106-126. 45 A previous study found that NAMI-A effectively inhibited the aggregation of PrP106-126, but it lacked cytotoxicity data and in-depth comparison with other complexes of similar molecular configuration.…”

Section: Introductionmentioning

confidence: 99%

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Inhibitory effects of NAMI-A-like ruthenium complexes on prion neuropeptide fibril formation

et al. 2015

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Prion diseases are a group of infectious and fatal neurodegenerative disorders caused by the conformational conversion of a cellular prion protein (PrP) into its abnormal isoform PrP(Sc). PrP106-126 resembles PrP(Sc) in terms of physicochemical and biological characteristics and is used as a common model for the treatment of prion diseases. Inhibitory effects on fibril formation and neurotoxicity of the prion neuropeptide PrP106-126 have been investigated using metal complexes as potential inhibitors. Nevertheless, the binding mechanism between metal complexes and the peptide remains unclear. The present study is focused on the interaction of PrP106-126 with NAMI-A and NAMI-A-like ruthenium complexes, including KP418, KP1019, and KP1019-2. Results demonstrated that these ruthenium complexes could bind to PrP106-126 in a distinctive binding mode through electrostatic and hydrophobic interactions. NAMI-A-like ruthenium complexes can also effectively inhibit the aggregation and fibril formation of PrP106-126. The complex KP1019 demonstrated the optimal inhibitory ability upon peptide aggregation, and cytotoxicity because of its large aromatic ligand contribution. The studied complexes could also regulate the copper redox chemistry of PrP106-126 and effectually inhibit the formation of reactive oxygen species. Given these findings, ruthenium complexes with relatively low cellular toxicity may be used to develop potential pharmaceutical products against prion diseases.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Nami-a-like Ruthenium Complexes Bind To Prp106-126mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Inhibitory effects of NAMI-A-like ruthenium complexes on prion neuropeptide fibril formation

et al. 2015

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Transition Metal Complexes as Therapeutics: A New Frontier in Combatting Neurodegenerative Disorders through Protein Aggregation Modulation

Navale,

Ahmed,

Lim

et al. 2024

Adv Healthcare Materials

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Neurodegenerative disorders (NDDs) are a class of debilitating diseases that progressively impair the protein structure and result in neurological dysfunction in the nervous system. Among these disorders, Alzheimer's disease (AD), prion diseases such as Creutzfeldt‐Jakob disease (CJD), and Parkinson's disease (PD) are caused by protein misfolding and aggregation at the cellular level. In recent years, transition metal complexes have gained significant attention for their potential applications in diagnosing, imaging, and curing these NDDs. These complexes have intriguing possibilities as therapeutics due to their diverse ligand systems and chemical properties and can interact with biological systems with minimal detrimental effects. This review focuses on the recent progress in transition metal therapeutics as a new era of hope in the battle against AD, CJD, and PD by modulating protein aggregation in vitro and in vivo. It may shed revolutionary insights into unlocking new opportunities for researchers to develop metal‐based drugs to combat NDDs.

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Regulation of the aggregation behavior of human islet amyloid polypeptide fragment by titanocene complexes

Gong

2017

J Biol Inorg Chem

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The aggregation of human islet amyloid polypeptide (hIAPP) is associated with type II diabetes. The misfolding of hIAPP induces amyloid deposition and causes β-cell dysfunction. Metal complexes are potential metallodrugs that may reverse the aggregation of amyloid peptides. hIAPP19-37 is a crucial fragment of the full-length hIAPP1-37 and contains typical aromatic residues and a core hydrophobic region. In this work, we studied the effects of titanocene complexes titanocene dichloride (1), titanocene salicylic acid complex (2), and titanocene methionine complex (3) on the aggregation behavior of hIAPP19-37. We also explored the possible interactions of these complexes with hIAPP19-37. Results demonstrated that the titanocene complexes could effectively inhibit the aggregation of hIAPP19-37. The complexes bound with hIAPP19-37 in a spontaneous and exothermic process through hydrophobic interaction. Moreover, complex 3 could significantly decrease the cytotoxicity of hIAPP19-37 and improve cell survival. These data provide a basis for the use of titanocene complexes as potential agents against amyloidosis.

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Inhibition of human prion neuropeptide PrP106-126 aggregation by hexacoordinated ruthenium complexes

Cited by 19 publications

References 50 publications

Inhibitory effects of NAMI-A-like ruthenium complexes on prion neuropeptide fibril formation

Inhibitory effects of NAMI-A-like ruthenium complexes on prion neuropeptide fibril formation

Transition Metal Complexes as Therapeutics: A New Frontier in Combatting Neurodegenerative Disorders through Protein Aggregation Modulation

Regulation of the aggregation behavior of human islet amyloid polypeptide fragment by titanocene complexes

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