Metal complexes of modified cyclen as catalysts for hydrolytic restriction of plasmid DNA

Krauser, Joel A.; Joshi, Aarti; Kady, Ismail O.

doi:10.1016/j.jinorgbio.2010.04.007

Cited by 14 publications

(5 citation statements)

References 37 publications

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“…21,46,47 Therefore, the design of efficient, environment friendly, and economical mimics of metallohydrolases is extremely beneficial. 5,10,21,41,46,[48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63] In this review, activities of two bioinspired synthetic analogues such as polyoxometalates (POMs, I P ), and 1,4,7,10-tetraazacyclododecane (cyclen, I C ) and their analogues that similar to IDE and GpdQ lack substrate specificity are also discussed (Figure 1). Recently, I P complexes have been proposed as novel artificial metalloproteases and nucleases.…”

Section: Peptide and Phosphoester Hydrolysismentioning

confidence: 99%

“…That could be due to their high costs, challenging synthesis, broad specificities and small functioning temperature and pH ranges . Therefore, the design of efficient, environment friendly, and economical mimics of metallohydrolases is extremely beneficial . In this review, activities of two bioinspired synthetic analogues such as polyoxometalates (POMs, I P ), and 1,4,7,10‐tetraazacyclododecane (cyclen, I C ) and their analogues that similar to IDE and GpdQ lack substrate specificity are also discussed (Figure ).…”

Section: Introductionmentioning

confidence: 99%

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Mechanisms of peptide and phosphoester hydrolysis catalyzed by two promiscuous metalloenzymes (insulin degrading enzyme and glycerophosphodiesterase) and their synthetic analogues

Jayasinghe‐Arachchige

Sharma

et al. 2020

WIREs Comput Mol Sci

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The hydrolysis of extremely stable peptide and phosphoester bonds by metalloenzymes is of great interest in biotechnology and industry. However, due to various shortcomings only a handful of these enzymes have been used for industrial applications. Therefore, in the last two decades intensive scientific efforts have been made in rational development of small molecules to imitate the activities of natural enzymes. Despite these efforts, their currently available synthetic analogues are inferior in terms of selectivity, catalytic rate, and turnover and the designing of efficient artificial metalloenzymes remains a distant goal. This is a challenging area of research that necessitates a rigorous integration between experiments and theory. The realization of this goal requires knowledge of the catalytic activities of both enzymes and their existing analogues and an effective fusion of that knowledge. This article reviews several studies in which a plethora of computational techniques have been successfully employed to investigate the functioning of two chemically promiscuous mono‐ and binuclear metalloenzymes (insulin degrading enzyme and glycerophosphodiesterase) and two synthetic analogues. These studies will help us derive fundamental principles of peptide and phosphoester hydrolysis and pave the way to design efficient small molecule catalysts for these reactions. This article is categorized under: Structure and Mechanism > Reaction Mechanisms and Catalysis

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Section: Peptide and Phosphoester Hydrolysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mechanisms of peptide and phosphoester hydrolysis catalyzed by two promiscuous metalloenzymes (insulin degrading enzyme and glycerophosphodiesterase) and their synthetic analogues

Jayasinghe‐Arachchige

Sharma

et al. 2020

WIREs Comput Mol Sci

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“…A strong dependence of nuclease activity on the length of the spacer was also recently reported by I. O. Kady and co-workers in a family of cyclen-acridine conjugates. 58 The nature of the intercalator is also important. Using Zn(II)-binding-peptide-tethered intercalators, J. K. Barton et al reported substantial differences in reactivity.…”

Section: Metal Complexes-dna Binders Conjugatesmentioning

confidence: 99%

Progress in artificial metallonucleases

2012

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The development of synthetic agents able to hydrolytically cleave DNA with high efficiency and selectivity is still a fascinating challenge. Over the years, many examples have been reported reproducing part of the behaviour of the corresponding natural enzymes. Eventually, even the possibility to apply such systems to the manipulation of DNA of higher organisms has been demonstrated. However, efficiency of enzymes is still unrivalled. This feature article discusses the progress reported toward the realization of synthetic nucleases with particular attention to the comprehension of the reaction mechanisms and to the strategies that need to be addressed to obtain more efficient systems.

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“…Although these enzymes exhibit remarkable activities, they suffer from several limitations such as undesirable selectivity, difficulties in extraction or synthesis, high cost and narrow functional temperature, and pH range (Kövári and Krämer, 1996; Cowan, 2001; Mancin et al, 2012). Therefore, in the last couple of decades, intensive efforts have been made to design small metal complexes as synthetic analogs of natural enzymes for phosphoester hydrolysis (Burstyn and Deal, 1993; Hegg and Burstyn, 1998; Komiyama and Sumaoka, 1998; Blaskó and Bruice, 1999; Williams et al, 1999; Sreedhara and Cowan, 2001; Deck et al, 2002; Mitić et al, 2006; Niittymaki and Lonnberg, 2006; Bonomi et al, 2008; Krauser et al, 2010; Mancin et al, 2012; Daver et al, 2016; Sullivan et al, 2018). These analogs can offer multiple advantages over natural enzymes in terms of cost, size, and functionality (Weston, 2005; Yoji et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Effects of the Metal Ion on the Mechanism of Phosphodiester Hydrolysis Catalyzed by Metal-Cyclen Complexes

Jayasinghe‐Arachchige

Zuchniarz

et al. 2019

Front. Chem.

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In this study, mechanisms of phosphodiester hydrolysis catalyzed by six di- and tetravalent metal-cyclen ( M-C ) complexes ( Zn-C, Cu-C, Co-C, Ce-C, Zr-C and Ti-C ) have been investigated using DFT calculations. The activities of these complexes were studied using three distinct mechanisms: (1) direct attack ( DA ), (2) catalyst-assisted ( CA ), and (3) water-assisted ( WA ). All divalent metal complexes ( Zn-C, Cu-C and Co-C ) coordinated to the BNPP substrate in a monodentate fashion and activated its scissile phosphoester bond. However, all tetravalent metal complexes ( Ce-C, Zr-C , and Ti-C ) interacted with BNPP in a bidentate manner and strengthened this bond. The DA mechanism was energetically the most feasible for all divalent M-C complexes, while the WA mechanism was favored by the tetravalent complexes, except Ce-C . The divalent complexes were found to be more reactive than their tetravalent counterparts. Zn-C catalyzed the hydrolysis with the lowest barrier among all M-C complexes, while Ti-C was the most reactive tetravalent complex. The activities of Ce-C and Zr-C , except Ti-C , were improved with an increase in the coordination number of the metal ion. The structural and mechanistic information provided in this study will be very helpful in the development of more efficient metal complexes for this critical reaction.

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Metal complexes of modified cyclen as catalysts for hydrolytic restriction of plasmid DNA

Cited by 14 publications

References 37 publications

Mechanisms of peptide and phosphoester hydrolysis catalyzed by two promiscuous metalloenzymes (insulin degrading enzyme and glycerophosphodiesterase) and their synthetic analogues

Mechanisms of peptide and phosphoester hydrolysis catalyzed by two promiscuous metalloenzymes (insulin degrading enzyme and glycerophosphodiesterase) and their synthetic analogues

Progress in artificial metallonucleases

Effects of the Metal Ion on the Mechanism of Phosphodiester Hydrolysis Catalyzed by Metal-Cyclen Complexes

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