Platinum(II) coordination to N1 and N7,N1 of guanine: cis-DDP model cross-links in the interior and simultaneous cross-links at the periphery and the interior of DNA

Frommer, Gudrun; Mutikainen, Ilpo; Pesch, Ferdinand J.; Hillgeris, Edda C.; Preut, H.; Lippert, Bernhard

doi:10.1021/ic00038a024

Cited by 42 publications

(18 citation statements)

References 4 publications

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“…9c). 51,52 These complexes exhibit significantly increased p K a s at N7 of 4–5. If [4Fe–4S] clusters have similar effects, the binding of GTP to the C-terminal [4Fe–4S] cluster would facilitate protonation at N-7 (Fig.…”

Section: The Spasm–twitch Familymentioning

confidence: 97%

“…9b). Since neither protonation of O-6 nor the enol tautomer were observed in the Pt(II) complex, 51 it is likely that the guanine base is in the keto tautomer. The location of O-6 in the keto form is consistent with H-bonding interaction with the two catalytically essential Arg residues, R266 and R268.…”

Section: The Spasm–twitch Familymentioning

confidence: 99%

“…9c). 51,52 Protonation of N-7 of GTP in the MoaA active site at the physiological pH likely requires additional assistance from the environment around N-7. While the MoaA crystal structure does not reveal specific residues around N-7 that could stabilize the protonated form, 45,46 recent studies revealed that the C-terminal tail, which is disordered in the crystal structures, is likely serving as part of the active site.…”

Section: The Spasm–twitch Familymentioning

confidence: 99%

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C–C bond forming radical SAM enzymes involved in the construction of carbon skeletons of cofactors and natural products

Yokoyama

Lilla

2018

Nat. Prod. Rep.

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C–C bond formations are frequently the key steps in cofactor and natural product biosynthesis. Historically, C–C bond formations were thought to proceed by two electron mechanisms, represented by Claisen condensation in fatty acids and polyketide biosynthesis. These types of mechanisms require activated substrates to create a nucleophile and an electrophile. More recently, increasing number of C–C bond formations catalyzed by radical SAM enzymes are being identified. These free radical mediated reactions can proceed between almost any sp3 and sp2 carbon centers, allowing introduction of C–C bonds at unconventional positions in metabolites. Therefore, free radical mediated C–C bond formations are frequently found in the construction of structurally unique and complex metabolites. This review discusses our current understanding of the functions and mechanisms of C–C bond forming radical SAM enzymes and highlights their important roles in the biosynthesis of structurally complex, naturally occurring organic molecules. Mechanistic consideration of C–C bond formation by radical SAM enzymes identifies the significance of three key mechanistic factors: radical initiation, acceptor substrate activation and radical quenching. Understanding the functions and mechanisms of these characteristic enzymes will be important not only in promoting our understanding of radical SAM enzymes, but also for understanding natural product and cofactor biosynthesis.

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Section: The Spasm–twitch Familymentioning

confidence: 97%

Section: The Spasm–twitch Familymentioning

confidence: 99%

Section: The Spasm–twitch Familymentioning

confidence: 99%

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C–C bond forming radical SAM enzymes involved in the construction of carbon skeletons of cofactors and natural products

Yokoyama

Lilla

2018

Nat. Prod. Rep.

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“…In one case, even both forms coexist in a single Pt II complex. [31] Similar examples exist for guanine [32] and adenine nucleobases, [33] and the rare 4-hydroxo-2-oxo tautomer of 1-methyluracil has likewise been isolated as a metalstabilized form.…”

Section: Discussionmentioning

confidence: 73%

Isocytosine as a Hydrogen‐Bonding Partner and as a Ligand in Metal Complexes

Gupta¹,

Roitzsch²,

Lippert³

2005

Chemistry A European J

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Isocytosine (ICH; 1) exists in solution in an equilibrium of tautomers 1a and 1b with the N1 and N3 positions carrying the acidic proton, respectively. In the solid state, both tautomers coexist in a 1:1 ratio. As we show, the N3H tautomer 1b can selectively be crystallized in the presence of the model nucleobase 1-methylcytosine (1-MeC). The complex 1b x (1-MeC)2 x H2O (2) forms pairs through three hydrogen bonds between the components; hydrogen bonds between identical molecules are also formed, leading to an infinite tape structure. On the other hand, the N1H tautomer 1a co-crystallizes with protonated ICH to give [1a x ICH2]NO3 (3), again with three hydrogen bonds between the partners, yet the acidic proton is disordered over the two entities. With M(II)(dien) (M=Pt, Pd; dien=diethylenetriamine) preferential coordination of tautomer 1a through the N3 position is observed. DFT calculations, which were also extended to Pt(II)(tmeda) linkage isomers (tmeda=N,N,N',N'-tetramethylethylenediamine), suggest that intramolecular hydrogen bonding between the ICH tautomers and the co-ligands at M, while adding to the preference for N3 coordination, is not the major determining factor. Rather it is the inherently stronger Pt-N3 bond which favors complexation of 1a. With an excess of M(II)(dien), dinuclear species [M2(dien)2(IC-N1,N3)]3+ (M=Pd(II), 4 and Pt(II), 5) also form and were isolated as their ClO4(-) salts and structurally characterized. In strongly acidic medium 5 is converted to [Pt(dien)(ICH-N1)]2+ (6), that is, to the Pt(II) complex of tautomer 1b.

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“…Metal binding to such sites thus "forces" the proton to bind to another nucleobase site and leads to the generation of a species which we have termed "metal-stabilized rare tautomer" (Scheme 2). Representations of this second type have been synthesized for the common model nucleobases 9-methyladenine, [9] 9-alkylguanine, [10] 1-methylcytosine, [11] 1-methyluracil, [12] and 1-methylthymine. [13] With unsubstituted parent nucleobases such as cytosine, [14] or thymine/uracil, [15] or related isocytosine, [16] metal complexes of individual tautomers have likewise been reported.…”

Section: (A)(b)(c)a C H T U N G T R E N N U N G (Oh 2 )]mentioning

confidence: 99%

Rare Tautomers of 1‐Methyluracil and 1‐Methylthymine: Tuning Relative Stabilities through Coordination to Pt^II Complexes

Wijst

Guerra

Swart

et al. 2008

Chemistry A European J

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We have computationally explored how the relative stabilities of 1-methyluracil (1-MeUH) tautomers can be tuned through coordination of these tautomers to Pt(II) complexes with a particular set of ligands. This has been done using density functional theory at the BP86/TZ2P level. Thus, we have examined the water/1-MeUH exchange reactions of [Pt(II)(A)(B)(C)(OH(2))](q) + 1-MeUH to uncover: i) which tautomers are best stabilized by the Pt(II) complex, and ii) how the net charge q in the complex affects the reaction energy. The net charge q depends on the ligands A, B, and C, which can be the neutral NH(3) or anionic Cl(-). To reveal the effect of solvation, all reaction systems are studied both in the gas phase and in water. Also the stabilization of tautomers of 1-methylthymine (1-MeTH) by cisplatin is investigated. The calculations reveal that relative energies of the metal (here: Pt(II))-complexed forms of the various tautomers (here: of 1-MeUH and 1-MeTH) do not parallel those of the free tautomers. Rather, a rare nucleobase tautomer, despite its low natural abundance, may become favored over the predominant one when complexed to a metal ion.

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Platinum(II) coordination to N1 and N7,N1 of guanine: cis-DDP model cross-links in the interior and simultaneous cross-links at the periphery and the interior of DNA

Cited by 42 publications

References 4 publications

C–C bond forming radical SAM enzymes involved in the construction of carbon skeletons of cofactors and natural products

C–C bond forming radical SAM enzymes involved in the construction of carbon skeletons of cofactors and natural products

Isocytosine as a Hydrogen‐Bonding Partner and as a Ligand in Metal Complexes

Rare Tautomers of 1‐Methyluracil and 1‐Methylthymine: Tuning Relative Stabilities through Coordination to Pt^II Complexes

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Platinum(II) coordination to N1 and N7,N1 of guanine: cis-DDP model cross-links in the interior and simultaneous cross-links at the periphery and the interior of DNA

Cited by 42 publications

References 4 publications

C–C bond forming radical SAM enzymes involved in the construction of carbon skeletons of cofactors and natural products

C–C bond forming radical SAM enzymes involved in the construction of carbon skeletons of cofactors and natural products

Isocytosine as a Hydrogen‐Bonding Partner and as a Ligand in Metal Complexes

Rare Tautomers of 1‐Methyluracil and 1‐Methylthymine: Tuning Relative Stabilities through Coordination to PtII Complexes

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Rare Tautomers of 1‐Methyluracil and 1‐Methylthymine: Tuning Relative Stabilities through Coordination to Pt^II Complexes