Reaction of [Pt(Gly-Gly-N,N′,O)I]− with the N-acetylated dipeptide l-methionyl-l-histidine: Selective platination of the histidine side chain by intramolecular migration of the platinum(II) complex

Živković, Marija D.; Rajković, Snežana; Djuran, Miloš I.

doi:10.1016/j.bioorg.2008.02.005

Cited by 8 publications

(5 citation statements)

References 19 publications

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“…However, cysteines are not present in a reduced form in IgGs. Moreover, model studies and density functional theory (DFT) calculations have shown that Pt-methionine bonds are labile and will become broken after the post-treatment with thiourea (38)(39)(40). Thus, the thermodynamically favored histidines are most likely to be the binding sites of platinum(II).…”

Section: Nci-n87mentioning

confidence: 99%

A Novel Platinum(II)–Based Bifunctional ADC Linker Benchmarked Using 89Zr-Desferal and Auristatin F–Conjugated Trastuzumab

Sijbrandi¹,

Merkul²,

Muns³

et al. 2017

Cancer Research

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Greater control is desirable in the stochastic conjugation technology used to synthesize antibody-drug conjugates (ADC). We have shown recently that a fluorescent dye can be stably conjugated to a mAb using a bifunctional platinum(II) linker. Here, we describe the general applicability of this novel linker technology for the preparation of stable and efficacious ADCs. The ethylenediamine platinum(II) moiety, herein called Lx, was coordinated to Desferal (DFO) or auristatin F (AF) to provide storable "semifinal" products, which were directly conjugated to unmodified mAbs. Conjugation resulted in ADCs with unimpaired mAb-binding characteristics, DAR in the range of 2.5 to 2.7 and approximately 85% payload bound to the Fc region, presumably to histidine residues. To evaluate the in vivo stability of Lx and its effect on pharmacokinetics and tumor targeting of an ADC, Lx-DFO was conjugated to the HER2 mAb trastuzumab, followed by radiolabeling with Zr. Trastuzumab-Lx-DFO-Zr was stable in vivo and exhibited pharmacokinetic and tumor-targeting properties similar to parental trastuzumab. In a xenograft mouse model of gastric cancer (NCI-N87) or an ado-trastuzumab emtansine-resistant breast cancer (JIMT-1), a single dose of trastuzumab-Lx-AF outperformed its maleimide benchmark trastuzumab-Mal-AF and FDA-approved ado-trastuzumab emtansine. Overall, our findings show the potential of the Lx technology as a robust conjugation platform for the preparation of anticancer ADCs. Cancer Res; 77(2); 257-67. ©2016 AACR.

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Section: Nci-n87mentioning

confidence: 99%

A Novel Platinum(II)–Based Bifunctional ADC Linker Benchmarked Using 89Zr-Desferal and Auristatin F–Conjugated Trastuzumab

Sijbrandi¹,

Merkul²,

Muns³

et al. 2017

Cancer Research

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“…Sisplatin yapısındaki taşıyıcı amonyak ligandının farklı heterosiklik amin grupları ile yer değiştirilmesi sonucunda rezinstans gelişen kanser türlerine karşı etkili olan veya hiç etki görülmeyen kanser türlerine karşı terapötik etkinliği artmış kompleks geliştirme çalışmaları hız kesmeden devam etmektedir [15][16][17][18][19]. Bu amaçla organizmanın tanıdığı çeşitli aminoasitler, glukozaminler ve peptidleri taşıyan veya endojen bileşiklerin biyoizosterleri taşıyıcı ligand olarak kullanılmaktadır [20][21][22].…”

Section: Introductionunclassified

“…Heteroaromatik bisiklik halka sistemine sahip olan benzimidazol, yapısında bulunan asidik ve bazik özelliğe sahip azot atomlarından dolayı amfoterik karakter göstermektedir. DNA yapı taşını oluşturan pürin bazlarına, birçok kofaktör, aminoasitler ve vitamin B12 gibi biyoaktif moleküllerinin yapısında bulunmasından dolayı organizmanın tanıdığı aromatik bir halka sistemidir [22][23][24][25]. Benzimidazol halka sistemine sahip ilaçların antikanser, antihelmintik, antifungal, antiviral, antienflamatuvar, antihistaminik, antipsikotik gibi terapötik etkinlikleri bulunmaktadır [25][26][27][28][29][30].…”

Section: Introductionunclassified

Synthesis and Investigation of the Anticancer Activities of Platin Complexes Bearing 2,5(6)-Disubstitutedbenzimidazole Derivative Ligands

ALJENDY

Demirbağ

BAYRAM

et al. 2023

Ankara Ecz. Fak. Derg.

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Amaç: Sisplatin, klinikte kanser hastalarının tedavisinde başarılı bir şekilde kullanılmasına rağmen hastalarda rezistans gelişimi ve ciddi toksik yan etkiler görülmektedir. Bu dezavantajların önüne geçmek için bu çalışmada 2,5(6)-disübstitüebenzimidazol türevi taşıyıcı ligandlar kullanarak platin(II) komplekslerinin sentezlenmesi ve sitotoksik etkilerinin test edilmesi amaçlanmıştır. Gereç ve Yöntem: L1-L6 taşıyıcı ligandları Philips yöntemine göre elde edilmiştir. K1-K4 kompleksleri, K2PtCl4 ve uygun ligandın ısıtılıp karıştırılması ile sentezlenmiştir. Sentez edilen L1-L6 ve K1-K4’ün kimyasal yapıları elementel analiz, İnfrared ve 1H Nükleer Manyetik Rezonans ile aydınlatılmıştır. L1-L6 taşıyıcı ligandları ve K1-K4 komplesklerinin, MTT yöntemi ile MCF-7 ve DU-145 hücre hatlarına karşı in vitro sitotoksik etkileri test edilmiştir. Sonuç ve Tartışma IC50 değerlerine göre 2 numaralı konumunda –CH3 sübstitüenti taşıyan ligandlar, nonsübstitüe ligandlara göre test edilen hücre hatlarında daha etkili bulunmuştur. Ayrıca 5(6) numaralı konumunda flor sübstitüe L5 ve L6 en etkili benzimidazol türevi olarak test edilmiştir. Test edilen kompleksler içerisinde K3, MCF-7 hücre hattına karşı 32.75 µM IC50 değeri ile DU-145 hücre hattında ise 18.842 µM IC50 değeri ile en etkili kompleks olarak bulunmuştur.

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“…Also, many of these drugs are resistant to some types of tumors. Recently, researchers addressed also some other transition metals, e.g., coordination compounds of Ru(II), , Pt(IV), , Ir(III), − and several others. − These substances can be often administrated in an inactive form being activated in an organism later. Among this family of drugs belongs also Pt(IV) complexes characterized by relatively high kinetic inertness.…”

Section: Introductionmentioning

confidence: 99%

Side Reactions with an Equilibrium Constraint: Detailed Mechanism of the Substitution Reaction of Tetraplatin with dGMP as a Starting Step of the Platinum(IV) Reduction Process

Šebesta

Burda

2017

J. Phys. Chem. B

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Two possible pathways of the substitution reaction within the reduction process of the Pt(DACH)Cl by dGMP are compared: associative reaction course and autocatalytic Basolo-Pearson mechanisms. Since two forms: single-protonated and fully deprotonated phosphate group of dGMP are present in equilibrium at neutral and mildly acidic solutions, consideration of a side reactions scheme with acido-basic equilibrium-constraint is a very important model for obtaining reliable results. The examined complexes are optimized at the B3LYP-GD3BJ/6-31G(d) level with the COSMO implicit solvation model and Klamt's radii used for cavity construction. Energy characteristics and thermodynamics for all reaction branches are determined using the B3LYP-GD3BJ/6-311++G(2df,2pd)/IEF-PCM/scaled-UAKS level with Wertz's entropy corrections. Rate constants are estimated for each individual branch according to Eyring's transition state theory (TST), averaged according to equilibrium constraint and compared with available experimental data. The determined reaction barriers of the autocatalytic pathway fairly correspond with experimental values. Furthermore, autocatalytic reaction of tetraplatin and its two analogues complexes [Pt(en)Cl and Pt(NH)Cl] are explored and compared with measured data in order to examined general reaction descriptors.

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Reaction of [Pt(Gly-Gly-N,N′,O)I]− with the N-acetylated dipeptide l-methionyl-l-histidine: Selective platination of the histidine side chain by intramolecular migration of the platinum(II) complex

Cited by 8 publications

References 19 publications

A Novel Platinum(II)–Based Bifunctional ADC Linker Benchmarked Using 89Zr-Desferal and Auristatin F–Conjugated Trastuzumab

A Novel Platinum(II)–Based Bifunctional ADC Linker Benchmarked Using 89Zr-Desferal and Auristatin F–Conjugated Trastuzumab

Synthesis and Investigation of the Anticancer Activities of Platin Complexes Bearing 2,5(6)-Disubstitutedbenzimidazole Derivative Ligands

Side Reactions with an Equilibrium Constraint: Detailed Mechanism of the Substitution Reaction of Tetraplatin with dGMP as a Starting Step of the Platinum(IV) Reduction Process

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