ChemInform Abstract: Targeting Nucleic Acids Using Dynamic Combinatorial Chemistry

ChemInform ◽  
2011 ◽  
Vol 42 (48) ◽  
pp. no-no
Author(s):  
Chandramathi R. Sherman Durai ◽  
Margaret M. Harding
Keyword(s):  
Nucleic Acids ◽  
Combinatorial Chemistry ◽  
Dynamic Combinatorial Chemistry

Evolutionary approaches for the discovery of functional synthetic small molecules

2006 ◽  
Vol 78 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Zev J. Gartner
Keyword(s):  
Genetic Algorithms ◽  
Nucleic Acids ◽  
Small Molecules ◽  
Directed Evolution ◽  
Functional Properties ◽  
Combinatorial Chemistry ◽  
Genetic Information ◽  
Powerful Method ◽  
Templated Synthesis ◽  
Dynamic Combinatorial Chemistry

Directed evolution is a powerful method for the laboratory discovery of nucleic acids and proteins with desired functional properties. A hallmark of this approach is the iterative translation, selection, amplification, and diversification of genetic information. The potential of evolutionary methods to impact the discovery of synthetic small molecules has recently been explored by a variety of laboratories. Four methods encompassing some or all of the hallmarks of evolution are discussed, including dynamic combinatorial chemistry (DCC), genetic algorithms (GAs), DNA display, and DNA-templated synthesis (DTS).

Targeting Nucleic Acids using Dynamic Combinatorial Chemistry

2011 ◽  
Vol 64 (6) ◽  
pp. 671 ◽  
Author(s):  
Chandramathi R. Sherman Durai ◽  
Margaret M. Harding
Keyword(s):  
Nucleic Acids ◽  
Combinatorial Chemistry ◽  
Self Assembly ◽  
Block Design ◽  
Quadruplex Dna ◽  
Dynamic Combinatorial Chemistry ◽  
Lead Compounds ◽  
Dna And Rna ◽  
Target Nucleic Acid ◽  
Dna Quadruplex

Dynamic combinatorial chemistry (DCC) is a powerful method for the identification of novel ligands for the molecular recognition of receptor molecules. The method relies on self-assembly processes to generate libraries of compounds under reversible conditions, allowing a receptor molecule to select the optimal binding ligand from the mixture. However, while DCC is now an established field of chemistry, there are limited examples of the application of DCC to nucleic acids. The requirement to conduct experiments under physiologically relevant conditions, and avoid reaction with, or denaturation of, the target nucleic acid secondary structure, limits the choice of the reversible chemistry, and presents restrictions on the building block design. This review will summarize recent examples of applications of DCC to the recognition of nucleic acids. Studies with duplex DNA, quadruplex DNA, and RNA have utilized mainly thiol disulfide libraries, although applications of imine libraries, in combination with metal coordination, have been reported. The use of thiol disulfide libraries produces lead compounds with limited biostability, and hence design of stable analogues or mimics is required for many applications.

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 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

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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