Discovering Biomolecules with <i>Huisgenase</i> Activity: Designed Repeat Proteins as Biocatalysts for (3 + 2) Cycloadditions

Rivilla, Iván; Odriozola-Gimeno, M.; Aires, Antonio; Gimeno, Ana; Jiménez‐Barbero, Jesús; Torrent‐Sucarrat, Miquel; Cortajarena, Aitziber L.; Cossío, Fernando P.

doi:10.1021/jacs.9b06823

Cited by 9 publications

(10 citation statements)

References 87 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…40 Finally, the exo′ product has been synthesized catalyzing the reaction with consensus tetratricopeptide repeat proteins in tetrahydrofuran solution, which generates the four pyrrolidine stereoisomers in equimolar ratio. 41 Our computational results for this reaction are fully consistent with previous studies. 40,41 Without the presence of an EEF, using a Boltzmann distribution over the activation energy barriers of the different cycloadducts obtained, the ratios 5.3:2.9:1.8:0 for the endo, exo, endo′, and exo′ are predicted, respectively.…”

Section: ■ Results and Discussionsupporting

confidence: 91%

“…When the reaction is carried out without solvent, both in thermal or microwave conditions, a mixture of exo, endo, and endo′ cycloadducts is obtained . Finally, the exo′ product has been synthesized catalyzing the reaction with consensus tetratricopeptide repeat proteins in tetrahydrofuran solution, which generates the four pyrrolidine stereoisomers in equimolar ratio …”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Fast and Simple Evaluation of the Catalysis and Selectivity Induced by External Electric Fields

et al. 2021

Self Cite

View full text Add to dashboard Cite

In the oriented external electric-field-driven catalysis, the reaction rates and the selectivity of chemical reactions can be tuned at will. The activation barriers of chemical reactions within external electric fields of several strengths and directions can be computationally modeled. However, the calculation of all of the required field-dependent transition states and reactants is computationally demanding, especially for large systems. Herein, we present a method based on the Taylor expansion of the field-dependent energy of the reactants and transition states in terms of their field-free dipole moments and electrical (hyper)polarizabilities. This approach, called field-dependent energy barrier (FDB β ), allows systematic onedimensional (1D), two-dimensional (2D), and three-dimensional (3D) representations of the activation energy barriers for any strength and direction of the external electric field. The calculation of the field-dependent FDB β energy barriers has a computational cost several orders of magnitude lower than the explicit electric field optimizations, and the errors of the FDB β barriers are within the range of only 1−2 kcal•mol −1 . The achieved accuracy is sufficient for a fast-screening tool to study and predict potential electric-fieldinduced catalysis, regioselectivity, and stereoselectivity. As illustrative examples, four cycloadditions (1,3-dipolar and Diels−Alder) are studied.

show abstract

Section: ■ Results and Discussionsupporting

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Fast and Simple Evaluation of the Catalysis and Selectivity Induced by External Electric Fields

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…In 2020, a group of researchers around Jiménez‐Barbero, A. L. Cortajarena, and F. P. Cossío were finally able to design a “Huisgenase” that is capable of catalyzing a (3+2) cycloaddition between azomethine ylides and nitroalkenes . In this enzymatic reaction between methyl N ‐benzylidene glycinate and ( E )‐nitrostyrene up to four racemic cycloadducts can be formed.…”

Section: Introductionmentioning

confidence: 99%

The Huisgen Reaction: Milestones of the 1,3‐Dipolar Cycloaddition

2020

View full text Add to dashboard Cite

The concept of 1,3‐dipolar cycloadditions was presented by Rolf Huisgen 60 years ago. Previously unknown reactive intermediates, for example azomethine ylides, were introduced to organic chemistry and the (3+2) cycloadditions of 1,3‐dipoles to multiple‐bond systems (Huisgen reaction) developed into one of the most versatile synthetic methods in heterocyclic chemistry. In this Review, we present the history of this research area, highlight important older reports, and describe the evolution and further development of the concept. The most important mechanistic and synthetic results are discussed. Quantum‐mechanical calculations support the concerted mechanism always favored by R. Huisgen; however, in extreme cases intermediates may be involved. The impact of 1,3‐dipolar cycloadditions on the click chemistry concept of K. B. Sharpless will also be discussed.

show abstract

“…In our view, future directions in the field of protein design point towards the achievement of fully synthetic catalytic systems. In this direction, engineered artificial proteins based on repeat proteins were shown to catalyze a (3+2) cycloaddition, a reaction not described to be catalyzed by any natural enzyme [57]. In addition, similarly to the synthesis of ArMs, protein-metal cluster hybrids with potential catalytic activity have been designed using the same repeat scaffolding protein [29].…”

Section: Protein Hybrid Bionanomaterials For Catalysismentioning

confidence: 99%

Protein-based functional hybrid bionanomaterials by bottom-up approaches

Beloqui

Cortajarena

2020

Current Opinion in Structural Biology

View full text Add to dashboard Cite

This review aims to summarize the last advances on the field of protein engineering towards functional bionanomaterials. Albeit being this an emerging research field, multidisciplinary perspectives in the design of synthetic protein-based hybrid bionanomaterials have resulted in significant progresses. The review covers the definition of bionanomaterials as such and the description of the main methodological approaches currently employed for their assembly. In this context, special emphasis is placed on the fundamental role of protein design. Then, a general overview of the most recent advances related to the fabrication and application of protein-based bionanomaterials in several applications is provided, with special focus on catalysis. Finally, key aspects to be considered by the research community to establish the path for significant future developments in this promising field are discussed.

show abstract

Discovering Biomolecules with Huisgenase Activity: Designed Repeat Proteins as Biocatalysts for (3 + 2) Cycloadditions

Cited by 9 publications

References 87 publications

Fast and Simple Evaluation of the Catalysis and Selectivity Induced by External Electric Fields

Fast and Simple Evaluation of the Catalysis and Selectivity Induced by External Electric Fields

The Huisgen Reaction: Milestones of the 1,3‐Dipolar Cycloaddition

Protein-based functional hybrid bionanomaterials by bottom-up approaches

Contact Info

Product

Resources

About