Cupin Variants as Macromolecular Ligand Library for Stereoselective Michael Addition of Nitroalkanes

2019 ◽  
Author(s):  
Nobutaka Fujieda ◽  
Miho Yuasa ◽  
Yosuke Nishikawa ◽  
Genji Kurisu ◽  
Shinobu Itoh ◽  
...  
Keyword(s):  
Michael Addition ◽  
In Silico ◽  
Addition Reaction ◽  
Single Point ◽  
Point Mutations ◽  
Unsaturated Ketone ◽  
Michael Addition Reaction ◽  
Beta Barrel ◽  
Cupin Superfamily ◽  
Single Point Mutations

Cupin superfamily proteins (TM1459) work as a macromolecular ligand framework with a double-stranded beta-barrel structure ligating to a Cu ion through histidine side chains. Variegating the first coordination sphere of TM1459 revealed that H52A and H54A/H58A mutants effectively catalyzed the diastereo- and enantio-selective Michael addition reaction of nitroalkanes to an α,β-unsaturated ketone. Moreover, in silico substrate docking signified C106N and F104W single-point mutations, which inverted the diastereoselectivity of H52A and further improved the stereoselectivity of H54A/H58A, respectively.

Cupin Variants as Macromolecular Ligand Library for Stereoselective Michael Addition of Nitroalkanes

2019 ◽  
Author(s):  
Nobutaka Fujieda ◽  
Haruna Ichihashi ◽  
Miho Yuasa ◽  
Yosuke Nishikawa ◽  
Genji Kurisu ◽  
...  
Keyword(s):  
Michael Addition ◽  
In Silico ◽  
Addition Reaction ◽  
Single Point ◽  
Point Mutations ◽  
Unsaturated Ketone ◽  
Michael Addition Reaction ◽  
Beta Barrel ◽  
Cupin Superfamily ◽  
Single Point Mutations

Cupin superfamily proteins (TM1459) work as a macromolecular ligand framework with a double-stranded beta-barrel structure ligating to a Cu ion through histidine side chains. Variegating the first coordination sphere of TM1459 revealed that H52A and H54A/H58A mutants effectively catalyzed the diastereo- and enantio-selective Michael addition reaction of nitroalkanes to an α,β-unsaturated ketone. Moreover, in silico substrate docking signified C106N and F104W single-point mutations, which inverted the diastereoselectivity of H52A and further improved the stereoselectivity of H54A/H58A, respectively.

scholarly journals Single point mutations can potentially enhance infectivity of SARS-CoV-2 revealed by in silico affinity maturation and SPR assay

2020 ◽  
Author(s):  
Ting Xue ◽  
Weikun Wu ◽  
Ning Guo ◽  
Chengyong Wu ◽  
Jian Huang ◽  
...  
Keyword(s):  
Binding Affinity ◽  
In Silico ◽  
Cell Attachment ◽  
Single Point ◽  
Point Mutations ◽  
Cell Receptor ◽  
Affinity Maturation ◽  
Promising Target ◽  
Assay Result ◽  
Single Point Mutations

AbstractThe RBD (receptor binding domain) of the SARS-CoV-2 virus S (spike) protein mediates the viral cell attachment and serves as a promising target for therapeutics development. Mutations on the S-RBD may alter its affinity to cell receptor and affect the potency of vaccines and antibodies. Here we used an in-silico approach to predict how mutations on RBD affect its binding affinity to hACE2 (human angiotensin-converting enzyme2). The effect of all single point mutations on the interface was predicted. SPR assay result shows that 6 out of 9 selected mutations can strengthen binding affinity. Our prediction has reasonable agreement with the previous deep mutational scan results and recently reported mutants. Our work demonstrated in silico method as a powerful tool to forecast more powerful virus mutants, which will significantly benefit for the development of broadly neutralizing vaccine and antibody.

In silico study of the human rhodopsin and meta rhodopsin II/S-arrestin complexes: Impact of single point mutations related to retina degenerative diseases

2008 ◽  
Vol 70 (4) ◽  
pp. 1133-1141 ◽  
Author(s):  
Leonardo Mokarzel-Falcón ◽  
Juan Alexander Padrón-García ◽  
Ramón Carrasco-Velar ◽  
Colin Berry ◽  
Luis A. Montero-Cabrera
Keyword(s):  
In Silico ◽  
Single Point ◽  
Point Mutations ◽  
Degenerative Diseases ◽  
In Silico Study ◽  
Single Point Mutations

Single-Point Mutations in Qβ Virus-like Particles Change Binding to Cells

2021 ◽  
Author(s):  
Marisa L. Martino ◽  
Stephen N. Crooke ◽  
Marianne Manchester ◽  
M.G. Finn
Keyword(s):  
Single Point ◽  
Point Mutations ◽  
Virus Like Particles ◽  
Single Point Mutations

Tandem Alkylation/Michael Addition Reaction of Dithiocarbamic Acids with Alkyl γ-Bromocrotonates: Access to Functionalized 1,3-Thiazolidine-2-thiones

Synthesis ◽  
2021 ◽  
Author(s):  
Azim Ziyaei Halimehjani ◽  
Petr Beier ◽  
Maryam Khalili Foumeshi ◽  
Ali Alaei ◽  
Blanka Klepetářová
Keyword(s):  
Amino Acids ◽  
Carbon Disulfide ◽  
Multicomponent Reaction ◽  
Michael Addition ◽  
Addition Reaction ◽  
Primary Amines ◽  
Oxidation Reactions ◽  
Michael Addition Reaction ◽  
Synthetic Utility ◽  
Reaction Proceeds

AbstractThiazolidine-2-thiones were prepared via a novel multicomponent reaction of primary amines (amino acids), carbon disulfide, and γ-bromocrotonates. The reaction proceeds via a domino alkylation/intramolecular Michael addition to provide the corresponding thiazolidine-2-thiones in high to excellent yields. By using diamines in this protocol, bis(thiazolidine-2-thiones) derivatives were synthesized. The synthetic utility of the adducts was demonstrated by hydrolysis, amidation, and oxidation reactions.

Bisphosphine catalyzed sequential [3 + 2] cycloaddition and Michael addition of ynones with benzylidenepyrazolones via dual α′,α′-C(sp3)–H bifunctionalization to construct cyclopentanone-fused spiro-pyrazolones

2018 ◽  
Vol 16 (48) ◽  
pp. 9461-9471 ◽  
Author(s):  
Jiayong Zhang ◽  
Zhiwei Miao
Keyword(s):  
Michael Addition ◽  
Addition Reaction ◽  
Michael Addition Reaction

A sequential [3 + 2] cycloaddition and Michael addition reaction of ynones with benzylidenepyrazolones afforded cyclopentanone-fused spiro-pyrazolones catalyzed by DPPB via dual α′,α′-C(sp3)–H bifunctionalization.

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