13076-43-2Relevant articles and documents
Bioorganometallic chemistry: Biocatalytic oxidation reactions with biomimetic NAD+/NADH co-factors and [Cp*Rh(bpy)H]+ for selective organic synthesis
Lutz, Jochen,Hollmann, Frank,Ho, The Vinh,Schnyder, Adrian,Fish, Richard H.,Schmid, Andreas
, p. 4783 - 4790 (2004)
The biocatalytic, regioselective hydroxylation of 2-hydroxybiphenyl to the corresponding catechol was accomplished utilizing the monooxygenase 2-hydroxybiphenyl 3-monooxygenase (HbpA). The necessary natural 1,4-dihydronicotinamde adenine dinucleotide (NAD
In situ formation of H2O2 for P450 peroxygenases
Paul, Caroline E.,Churakova, Ekaterina,Maurits, Elmer,Girhard, Marco,Urlacher, Vlada B.,Hollmann, Frank
, p. 5692 - 5696 (2014)
An in situ H2O2 generation approach to promote P450 peroxygenases catalysis was developed through the use of the nicotinamide cofactor analogue 1-benzyl-1,4-dihydronicotinamide (BNAH) and flavin mononucleotide (FMN). Final productivity could be enhanced due to higher enzyme stability at low H2O2 concentrations. The H2O2 generation represented the rate-limiting step, however it could be easily controlled by varying both FMN and BNAH concentrations. Further characterization can result in an optimized ratio of FMN/BNAH/O2/biocatalyst enabling high reaction rates while minimizing H2O2-related inactivation of the enzyme.
The macrocyclic host with four nicotineamide subunits: Hydride transfer from a dihydronicotineamide guest in water
Skog, Klas,Wennerstroem, Olof
, p. 4629 - 4632 (1995)
A new macrocyclic host has been synthesised from four nicotine amide units linked by two paraxylene groups and two chiral [R,R]-1,2-diaminocyclohexane groups. In this positively charged, tetravalent, D2-symmetric, water soluble host, the two paraxylene groups cooperate to form a hydrophobic cavity where small charged or polar guests can be bound. The host also forms a complex in water with N-benzyldihydronicotineamide in which a hydride ion is transferred from the guest to the host.
Inhibitors of nicotinamide: N -methyltransferase designed to mimic the methylation reaction transition state
Van Haren, Matthijs J.,Taig, Rebecca,Kuppens, Jilles,Sastre Tora?o, Javier,Moret, Ed E.,Parsons, Richard B.,Sartini, Davide,Emanuelli, Monica,Martin, Nathaniel I.
, p. 6656 - 6667 (2017)
Nicotinamide N-methyltransferase (NNMT) is an enzyme that catalyses the methylation of nicotinamide to form N′-methylnicotinamide. Both NNMT and its methylated product have recently been linked to a variety of diseases, suggesting a role for the enzyme as a therapeutic target beyond its previously ascribed metabolic function in detoxification. We here describe the systematic development of NNMT inhibitors derived from the structures of the substrates involved in the methylation reaction. By covalently linking fragments of the NNMT substrates a diverse library of bisubstrate-like compounds was prepared. The ability of these compounds to inhibit NNMT was evaluated providing valuable insights into the structural tolerances of the enzyme active site. These studies led to the identification of new NNMT inhibitors that mimic the transition state of the methylation reaction and inhibit the enzyme with activity on par with established methyltransferase inhibitors.
Transfer hydrogenations catalyzed by streptavidin-hosted secondary amine organocatalysts
Santi, Nicolò,Morrill, Louis C.,?widerek, Katarzyna,Moliner, Vicent,Luk, Louis Y. P.
, p. 1919 - 1922 (2021)
Here, the streptavidin-biotin technology was applied to enable organocatalytic transfer hydrogenation. By introducing a biotin-tethered pyrrolidine (1) to the tetrameric streptavidin (T-Sav), the resulting hybrid catalyst was able to mediate hydride transfer from dihydro-benzylnicotinamide (BNAH) to α,β-unsaturated aldehydes. Hydrogenation of cinnamaldehyde and some of its aryl-substituted analogues was found to be nearly quantitative. Kinetic measurements revealed that the T-Sav:1 assembly possesses enzyme-like behavior, whereas isotope effect analysis, performed by QM/MM simulations, illustrated that the step of hydride transfer is at least partially rate-limiting. These results have proven the concept thatT-Savcan be used to host secondary amine-catalyzed transfer hydrogenations.
Straightforward Regeneration of Reduced Flavin Adenine Dinucleotide Required for Enzymatic Tryptophan Halogenation
Ismail, Mohamed,Schroeder, Lea,Frese, Marcel,Kottke, Tilman,Hollmann, Frank,Paul, Caroline E.,Sewald, Norbert
, p. 1389 - 1395 (2019)
Flavin-dependent halogenases are known to regioselectively introduce halide substituents into aromatic moieties, for example, the indole ring of tryptophan. The process requires halide salts and oxygen instead of molecular halogen in the chemical halogena
Photocatalytic reduction of artificial and natural nucleotide co-factors with a chlorophyll-like tin-dihydroporphyrin sensitizer
Oppelt, Kerstin T.,W??, Eva,Stiftinger, Martin,Sch?fberger, Wolfgang,Buchberger, Wolfgang,Kn?r, Günther
, p. 11910 - 11922 (2013)
An efficient photocatalytic two-electron reduction and protonation of nicotine amide adenine dinucleotide (NAD+), as well as the synthetic nucleotide co-factor analogue N-benzyl-3-carbamoyl-pyridinium (BNAD +), powered by photons in the long-wavelength region of visible light (λirr > 610 nm), is demonstrated for the first time. This functional artificial photosynthetic counterpart of the complete energy-trapping and solar-to-fuel conversion primary processes occurring in natural photosystem I (PS I) is achieved with a robust water-soluble tin(IV) complex of meso-tetrakis(N-methylpyridinium)-chlorin acting as the light-harvesting sensitizer (threshold wavelength of λthr = 660 nm). In buffered aqueous solution, this chlorophyll-like compound photocatalytically recycles a rhodium hydride complex of the type [Cp*Rh(bpy)H]+, which is able to mediate regioselective hydride transfer processes. Different one- and two-electron donors are tested for the reductive quenching of the irradiated tin complex to initiate the secondary dark reactions leading to nucleotide co-factor reduction. Very promising conversion efficiencies, quantum yields, and excellent photosensitizer stabilities are observed. As an example of a catalytic dark reaction utilizing the reduction equivalents of accumulated NADH, an enzymatic process for the selective transformation of aldehydes with alcohol dehydrogenase (ADH) coupled to the primary photoreactions of the system is also demonstrated. A tentative reaction mechanism for the transfer of two electrons and one proton from the reductively quenched tin chlorin sensitizer to the rhodium co-catalyst, acting as a reversible hydride carrier, is proposed.
Investigating the Structure-Reactivity Relationships Between Nicotinamide Coenzyme Biomimetics and Pentaerythritol Tetranitrate Reductase
Tan, Zhuotao,Han, Yaoying,Fu, Yaping,Zhang, Xiaowang,Xu, Mengjiao,Na, Qi,Zhuang, Wei,Qu, Xudong,Ying, Hanjie,Zhu, Chenjie
supporting information, p. 103 - 113 (2021/10/07)
Ene reductases (ERs) are attractive biocatalysts in terms of their high enantioselectivity and expanded substrate scope. Recent works have proved that synthetic nicotinamide coenzyme biomimetics (NCBs) can be used as easily accessible alternatives to natural cofactors in ER-catalyzed reactions. However, the structure-reactivity relationships between NCBs and ERs and influence factors are still poorly understood. In this study, a series of C-5 methyl modified NCBs were synthesized and tested in the PETNR-catalyzed asymmetric reductions. The physicochemical properties of these NCBs including electrochemical properties, stability, and kinetic behavior were studied in detail. The results showed that hydrophobic interaction caused by the introduced methyl group contributed to the stabilization of binding conformation in enzyme active site, resulting in comparable catalytic activity with that of NADPH. Molecular dynamics and steered molecular dynamics simulations were further performed to explain the binding mechanism between PETNR and NCBs, which revealed that stable catalytic conformation, appropriate donor-acceptor distance and angle, as well as free dissociation energy are important factors affecting the activity of NCBs. (Figure presented.).
COMPOUNDS FOR PROMOTING FOLLICLE MATURATION
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Page/Page column 17, (2021/07/17)
Some analogues (eg. 3-carbamoyl-1-(tetrahydro-2H-pyran-4-yl)pyridin-1-ium, 3- carboxy-1-isopropylpyridin-1-ium, 1-benzyl-3-carbamoylpyridin-1-ium, 3-carbamoyl-1- methylpyridin-1-ium and cyclopamine) are disclosed to treat female infertility as the compounds increase the percentage of primary follicles relative to primordial follicles compared to control samples.
The visible-light-driven transfer hydrogenation of nicotinamide cofactors with a robust ruthenium complex photocatalyst
Chen, Fushan,Deng, Li,Dong, Wenjin,Tang, Jie,Xian, Mo,Zhao, Lijun
, p. 2279 - 2287 (2020/04/20)
The highly efficient regeneration of nicotinamide cofactors has been successfully achieved with a quantum yield (Φ) of 7.9 × 10-3via photocatalytic transfer hydrogenation in the presence of the ruthenium complex Ru(tpy)(biq)Cl2 (where tpy = 2,2′:6′,2′′-terpyridine and biq = 2,2′-bisquinoline). The photocatalytic system is not only highly efficient but also tolerant to amino acid residues. The combination of this photocatalyst with glutamate dehydrogenase enabled the controllable and efficient synthesis of l-glutamate to be realized. A mechanism involving light-induced ligand exchange, decarboxylation and hydride transfer has been proposed. Kinetic isotope experiments revealed that the decarboxylation of [Ru(tpy)(biq)HCOO]+ to [Ru(tpy)(biq)H]+ was the rate-determining step with a small apparent activation energy of 3.2 ± 0.4 kcal mol-1. The hydricity of [Ru(tpy)(biq)H]+ was estimated, via reaction equilibrium, to be 40 ± 3 kcal mol-1
