scholarly journals Characterization of imine reductases in reductive amination for the exploration of structure-activity relationships

2020 ◽  
Vol 6 (21) ◽  
pp. eaay9320 ◽  
Author(s):  
Sarah L. Montgomery ◽  
Ahir Pushpanath ◽  
Rachel S. Heath ◽  
James R. Marshall ◽  
Ulrike Klemstein ◽  
...  
Keyword(s):  
Asymmetric Synthesis ◽  
Reductive Amination ◽  
Chiral Amines ◽  
Sequence Motif ◽  
Sequence Structure ◽  
Reaction Conditions ◽  
Rational Engineering ◽  
Structure Activity ◽  
Imine Reduction

Imine reductases (IREDs) have shown great potential as catalysts for the asymmetric synthesis of industrially relevant chiral amines, but a limited understanding of sequence activity relationships makes rational engineering challenging. Here, we describe the characterization of 80 putative and 15 previously described IREDs across 10 different transformations and confirm that reductive amination catalysis is not limited to any particular subgroup or sequence motif. Furthermore, we have identified another dehydrogenase subgroup with chemoselectivity for imine reduction. Enantioselectivities were determined for the reduction of the model substrate 2-phenylpiperideine, and the effect of changing the reaction conditions was also studied for the reductive aminations of 1-indanone, acetophenone, and 4-methoxyphenylacetone. We have performed sequence-structure analysis to help explain clusters in activity across a phylogenetic tree and to inform rational engineering, which, in one case, has conferred a change in chemoselectivity that had not been previously observed.

scholarly journals Characterization of non-heme iron aliphatic halogenase WelO5* from Hapalosiphon welwitschii IC-52-3: Identification of a minimal protein sequence motif that confers enzymatic chlorination specificity in the biosynthesis of welwitindolelinones

2017 ◽  
Vol 13 ◽  
pp. 1168-1173 ◽  
Author(s):  
Qin Zhu ◽  
Xinyu Liu
Keyword(s):  
Biochemical Characterization ◽  
Structural Diversity ◽  
Heme Iron ◽  
Sequence Motif ◽  
Rational Engineering ◽  
Non Heme Iron ◽  
C Terminus ◽  
Signature Sequence

The in vitro biochemical characterization revealed that iron/2-oxoglutarate (Fe/2OG)-dependent aliphatic halogenase WelO5* in Hapalosiphon welwitschii IC-52-3 has an enhanced substrate specificity towards 12-epi-hapalindole C (1) in comparison to WelO5 in H. welwitschii UTEX B1830. This allowed us to define the origin of the varied chlorinated versus dechlorinated alkaloid structural diversity between the two welwitindolinone producers. Furthermore, this study, along with the recent characterization of the AmbO5 protein, collectively confirmed the presence of a signature sequence motif in the C-terminus of this newly discovered halogenase enzyme family that confers substrate promiscuity and specificity. These observations may guide the rational engineering and evolution of these proteins for biocatalyst application.

Asymmetric synthesis and in vivo/in vitro characterization of new hybrid anticonvulsants derived from (2,5-dioxopyrrolidin-1-yl)phenylacetamides

2021 ◽  
Vol 109 ◽  
pp. 104751
Author(s):  
Michał Abram ◽  
Anna Rapacz ◽  
Gniewomir Latacz ◽  
Bartłomiej Szulczyk ◽  
Justyna Kalinowska-Tłuścik ◽  
...  
Keyword(s):  
Asymmetric Synthesis ◽  
In Vitro Characterization

scholarly journals Characterization of the SARS‐CoV‐2 E Protein: Sequence, Structure, Viroporin and Inhibitors

2021 ◽  
Author(s):  
Yipeng Cao ◽  
Rui Yang ◽  
Imshik Lee ◽  
Wenwen Zhang ◽  
Jiana Sun ◽  
...  
Keyword(s):  
Protein Sequence ◽  
Sequence Structure ◽  
E Protein

scholarly journals Synthesis and Structural Characterization of (E)-4-[(2-Hydroxy-3-methoxybenzylidene)amino]butanoic Acid and Its Novel Cu(II) Complex

Molbank ◽  
10.3390/m1179 ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. M1179
Author(s):  
Eleftherios Halevas ◽  
Antonios Hatzidimitriou ◽  
Barbara Mavroidi ◽  
Marina Sagnou ◽  
Maria Pelecanou ◽  
...  
Keyword(s):  
Schiff Base ◽  
Gamma Aminobutyric Acid ◽  
X Ray Diffraction ◽  
Reaction Conditions ◽  
Polymeric Compound ◽  
Bridging Ligands ◽  
1H And 13C Nmr ◽  
One Dimensional ◽  
Ft Ir

A novel Cu(II) complex based on the Schiff base obtained by the condensation of ortho-vanillin with gamma-aminobutyric acid was synthesized. The compounds are physico-chemically characterized by elemental analysis, HR-ESI-MS, FT-IR, and UV-Vis. The complex and the Schiff base ligand are further structurally identified by single crystal X-ray diffraction and 1H and 13C-NMR, respectively. The results suggest that the Schiff base are synthesized in excellent yield under mild reaction conditions in the presence of glacial acetic acid and the crystal structure of its Cu(II) complex reflects an one-dimensional polymeric compound. The molecular structure of the complex consists of a Cu(II) ion bound to two singly deprotonated Schiff base bridging ligands that form a CuN2O4 chelation environment, and a coordination sphere with a disordered octahedral geometry.

scholarly journals Novel Acetohydrazide Pyrazole Derivatives: Design, Synthesis, Characterization and Antimicrobial Activity

2019 ◽  
Vol 31 (12) ◽  
pp. 2740-2744
Author(s):  
Anil Verma ◽  
Vinod Kumar ◽  
Ramesh Kataria ◽  
Joginder Singh
Keyword(s):  
Mass Spectrometry ◽  
Antimicrobial Activity ◽  
Antimicrobial Agents ◽  
Antimicrobial Activities ◽  
Pyrazole Derivatives ◽  
Reaction Conditions ◽  
Design Synthesis ◽  
Structure Activity ◽  
Electron Withdrawing Group ◽  
Sar Study

Eleven acetohydrazide linked pyrazole derivatives were designed and synthesized via condensation of acetohyadrazide with different substituted formyl pyrazole derivatives under mild reaction conditions. Synthesized compounds were characterized on the basis of IR, NMR (1H & 13C) and mass spectrometry. The antimicrobial activities of all the compounds were screened against four bacterial and two fungal strains. Among the synthesized compounds, three compounds viz. 6b, 6c and 6d were found as efficient antimicrobial agents in reference to the standard drugs viz. ciprofloxacin and amphotericin-B. Further, structure-activity relationship (SAR) study revealed that electron-withdrawing group enhances the antimicrobial potential of synthesized derivatives as compared to other groups present in the ring. Hence, among compounds 6b-c, compound 6d could be explored further against other microbes to prove its vitality.

Diffuse Reflectance FT-IR Characterization of Active Sites under Reaction Conditions: The Production of Oxygenates in the CO/H2 Reaction

1994 ◽  
Vol 48 (10) ◽  
pp. 1208-1212 ◽  
Author(s):  
J. J. Benítez ◽  
I. Carrizosa ◽  
J. A. Odriozola
Keyword(s):  
Infrared Spectra ◽  
Active Sites ◽  
Diffuse Reflectance ◽  
Reaction Conditions ◽  
In Situ Drifts ◽  
Ft Ir

The reactivity of a Lu2O3-promoted Rh/Al2O3 catalyst in the CO/H2 reaction is reported. Methane, heavier hydrocarbons, methanol, and ethanol are obtained. In situ DRIFTS has been employed to record the infrared spectra under the actual reaction conditions. The structure of the observed COads DRIFTS bands has been resolved into its components. The production of oxygenates (methanol and ethanol) has been correlated with the results of the deconvolution calculation. Specific sites for the production of methanol and ethanol in the CO/H2 reaction over a Rh,Lu2O3/Al2O3 catalyst are proposed.

Structure/Activity Characterization of Glucagon-Like Peptide-1

1994 ◽  
Vol 225 (3) ◽  
pp. 1151-1156 ◽  
Author(s):  
Baptist Gallwitz ◽  
Maike Witt ◽  
Gabriele Paetzold ◽  
Corinna Morys-Wortmann ◽  
Bodo Zimmermann ◽  
...  
Keyword(s):  
Structure Activity ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Carbonyl catalysis enables a biomimetic asymmetric Mannich reaction

Science ◽  
2018 ◽  
Vol 360 (6396) ◽  
pp. 1438-1442 ◽  
Author(s):  
Jianfeng Chen ◽  
Xing Gong ◽  
Jianyu Li ◽  
Yingkun Li ◽  
Jiguo Ma ◽  
...  
Keyword(s):  
Asymmetric Synthesis ◽  
High Activity ◽  
Asymmetric Catalysis ◽  
Carbonyl Group ◽  
Mannich Reaction ◽  
Primary Amine ◽  
Chiral Amines ◽  
Carbonyl Groups ◽  
Diphenylphosphinyl Imines

Chiral amines are widely used as catalysts in asymmetric synthesis to activate carbonyl groups for α-functionalization. Carbonyl catalysis reverses that strategy by using a carbonyl group to activate a primary amine. Inspired by biological carbonyl catalysis, which is exemplified by reactions of pyridoxal-dependent enzymes, we developed an N-quaternized pyridoxal catalyst for the asymmetric Mannich reaction of glycinate with aryl N-diphenylphosphinyl imines. The catalyst exhibits high activity and stereoselectivity, likely enabled by enzyme-like cooperative bifunctional activation of the substrates. Our work demonstrates the catalytic utility of the pyridoxal moiety in asymmetric catalysis.

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