Development and mechanistic studies of an optimized receptor for trimethyllysine using iterative redesign by dynamic combinatorial chemistry

2014 ◽  
Vol 12 (36) ◽  
pp. 7059-7067 ◽  
Author(s):  
Nicholas K. Pinkin ◽  
Marcey L. Waters
Keyword(s):  
Thermodynamic Analysis ◽  
Combinatorial Chemistry ◽  
Mechanistic Studies ◽  
Dynamic Combinatorial Chemistry ◽  
Peptide Receptor ◽  
Insight Into

Iterative monomer redesign leads to a Kme3-peptide receptor with 10-fold tighter affinity and 5-fold improved selectivity over Kme2 than the original receptor. Thermodynamic analysis provides insight into this improvement.

Formation and Trapping of the Thermodynamically Unfavoured Inverted-Hemicucurbit[6]uril

2019 ◽  
Author(s):  
Elena Prigorchenko ◽  
Sandra Kaabel ◽  
Triin Narva ◽  
Anastassia Baškir ◽  
Maria Fomitšenko ◽  
...  
Keyword(s):  
Complex Formation ◽  
Combinatorial Chemistry ◽  
Trifluoroacetic Acid ◽  
Chloride Anion ◽  
Binding Affinities ◽  
Dynamic Covalent Chemistry ◽  
Reaction Selectivity ◽  
Low Concentration ◽  
Dynamic Combinatorial Chemistry ◽  
First Time

Amplification of a thermodynamically unfavoured macrocyclic product through the directed shift of the equilibrium between dynamic covalent chemistry library members is difficult to achieve. We show for the first time that during condensation of formaldehyde and <i>cis</i>-<i>N,N'</i>-cyclohexa-1,2-diylurea formation of <i>inverted-cis</i>-cyclohexanohemicucurbit[6]uril (<i>i-cis</i>-cycHC[6]) can be induced at the expense of thermodynamically favoured <i>cis</i>-cyclohexanohemicucurbit[6]uril (<i>cis</i>-cycHC[6]). The formation of <i>i-cis-</i>cycHC[6] is enhanced in low concentration of the templating chloride anion and suppressed in excess of this template. We found that reaction selectivity is governed by the solution-based template-aided dynamic combinatorial chemistry and continuous removal of the formed cycHC[6] macrocycles from the equilibrating solution by precipitation. Notably, the <i>i-cis</i>-cycHC[6] was isolated with 33% yield. Different binding affinities of three diastereomeric <i>i-cis</i>-, <i>cis</i>-cycHC[6] and their chiral isomer (<i>R,R</i>)-cycHC[6] for trifluoroacetic acid demonstrate the influence of macrocycle geometry on complex formation.

scholarly journals Insight into the mechanism of thermostabilization of GH10 xylanase from Bacillus sp. strain TAR-1 by the mutation of S92 to E

2021 ◽  
Vol 85 (2) ◽  
pp. 386-390
Author(s):  
Manami Suzuki ◽  
Teisuke Takita ◽  
Kohei Kuwata ◽  
Kota Nakatani ◽  
Tongyang Li ◽  
...  
Keyword(s):  
Amino Acid ◽  
Thermodynamic Analysis ◽  
Thermal Inactivation ◽  
Entropy Change ◽  
Crystallographic Analysis ◽  
Bacillus Sp ◽  
Amino Acid Residues ◽  
Gh10 Xylanase ◽  
Insight Into

ABSTRACT The mechanism of thermostabilization of GH10 xylanase, XynR, from Bacillus sp. strain TAR-1 by the mutation of S92 to E was investigated. Thermodynamic analysis revealed that thermostabilization was driven by the decrease in entropy change of activation for thermal inactivation. Crystallographic analysis suggested that this mutation suppressed the fluctuation of the amino acid residues at position 92-95.

scholarly journals Adventures in molecular recognition. The ins and outs of templating

2000 ◽  
Vol 72 (12) ◽  
pp. 2265-2274 ◽  
Author(s):  
Jeremy K. M. Sanders
Keyword(s):  
Molecular Recognition ◽  
Combinatorial Chemistry ◽  
Biological Systems ◽  
Design Approach ◽  
Supramolecular Systems ◽  
Disulfide Exchange ◽  
Dynamic Combinatorial Chemistry ◽  
Evolutionary Features ◽  
Selection Approach ◽  
Porphyrin Dimers

Two different approaches are described for the creation of supramolecular systems potentially capable of recognition and catalysis. Using the design approach, we have been able to accelerate and influence two different Diels­Alder reactions within the cavities of porphyrin dimers and trimers; this is templating from the outside inwards. The selection approach is a synthetic chemical attempt to capture some of the key evolutionary features of biological systems: dynamic combinatorial chemistry is used to create equilibrating mixtures of potential receptors, and then a template is used to select and amplify the desired system. Five potential reactions for such dynamic chemistry are discussed: base-catalyzed transesterification, hydrazone exchange, disulfide exchange, alkene metathesis, and Pd-catalyzed allyl exchange, and preliminary templating results (inside outwards) are presented.

Structure-Based Design of Inhibitors of the Aspartic Protease Endothiapepsin by Exploiting Dynamic Combinatorial Chemistry

2014 ◽  
Vol 53 (12) ◽  
pp. 3259-3263 ◽  
Author(s):  
Milon Mondal ◽  
Nedyalka Radeva ◽  
Helene Köster ◽  
Ahyoung Park ◽  
Constantinos Potamitis ◽  
...  
Keyword(s):  
Combinatorial Chemistry ◽  
Aspartic Protease ◽  
Dynamic Combinatorial Chemistry

Hydridosilylamido complexes of Ta and Mo isolobal with Berry's zirconocenes: syntheses, β-Si–H agostic interactions, catalytic hydrosilylation, and insight into mechanism

2016 ◽  
Vol 45 (6) ◽  
pp. 2554-2561 ◽  
Author(s):  
Nicolas A. McLeod ◽  
Lyudmila G. Kuzmina ◽  
Ilia Korobkov ◽  
Judith A. K. Howard ◽  
Georgii I. Nikonov
Keyword(s):  
Resting State ◽  
Mechanistic Studies ◽  
Catalytic Hydrosilylation ◽  
Insight Into

The β-SiH agostic complex (ArN)2Mo{η3-N(tBu)SiMe2–H}H is a pre-catalyst for hydrosilylation of carbonyls. Mechanistic studies revealed a non-hydride mechanism, with the benzoxy complex 8 being the resting state.

Dynamic combinatorial chemistry with diselenides and disulfides in water

2014 ◽  
Vol 50 (28) ◽  
pp. 3716-3718 ◽  
Author(s):  
Brian Rasmussen ◽  
Anne Sørensen ◽  
Henrik Gotfredsen ◽  
Michael Pittelkow
Keyword(s):  
Combinatorial Chemistry ◽  
Reversible Reaction ◽  
Dynamic Combinatorial Chemistry

Diselenide exchange is introduced as a reversible reaction in dynamic combinatorial chemistry in water at physiological pH.

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