RNA-directed off/on switch of RNase H activity using boronic ester formation

2017 ◽  
Vol 15 (38) ◽  
pp. 8204-8210 ◽  
Author(s):  
Maëva Reverte ◽  
Ivan Barvik ◽  
Jean-Jacques Vasseur ◽  
Michael Smietana
Keyword(s):  
Boronic Acid ◽  
Rnase H ◽  
Boronic Ester ◽  
Ester Formation

A new concept to modulate RNase H activity is presented based on the boronic acid/boronate switch.

scholarly journals Automated synthesis of 18F radiolabelled indole containing Oncrasin-like molecules; a comparison of iodonium salts and boronic ester chemistry.

2020 ◽  
Author(s):  
Alexander Franklin McDonald ◽  
Yit Woo Goh ◽  
Jonathan M White ◽  
Andrew M Scott ◽  
Uwe Ackermann
Keyword(s):  
Boronic Acid ◽  
Radiochemical Purity ◽  
Mutant Cell ◽  
Salt Formation ◽  
Malignant Tumours ◽  
Iodonium Salts ◽  
Boronic Ester ◽  
Iodonium Salt ◽  
Kras Protein

Abstract Background: Oncrasin-1 is a small molecule which was identified from a screen of KRAS mutant cancer cells and has shown specificity for KRAS mutant cell killing. We aimed to develop a radiolabelled form of Oncrasin-1 to enable in-vivo imaging of mutant KRAS expression in malignant tumours. This work outlines the synthesis of 3 fluorinated derivatives and development of iodonium salt and boronic ester precursors for radiolabelling with the 18F isotope. Results: In our hands, synthesis of iodonium salts were not easily accessible due to the 3-carbaldehyde indole structure being preferentially oxidized by conditions required for iodonium salt formation, rather than benzyl iodide. Synthesis and radiolabelling of boronic acid pinacol ester precursors were successful, with the products being obtained in yields of 10.76% ± 0.96% (n=5), 14.7% ±8.58% (n=3) and 14.92% ±3.9% (n=3) for 18F KAM001, 18F KAM002 and 18F KAM003 respectively, with radiochemical purity of greater than 99%.Conclusions: The successful synthesis of these tracers has been undertaken utilizing boronic ester radio-fluorination methods and will allow for investigation of Oncrasin based molecules as potential diagnostics for cancers expressing mutant KRAS protein.

scholarly journals Automated synthesis of 18F radiolabelled indole containing Oncrasin-like molecules; a comparison of iodonium salts and boronic ester chemistry.

2020 ◽  
Author(s):  
Alexander Franklin McDonald ◽  
Yit Wooi Goh ◽  
Jonathan M White ◽  
Andrew M Scott ◽  
Uwe Ackermann
Keyword(s):  
Boronic Acid ◽  
Radiochemical Purity ◽  
Mutant Cell ◽  
Salt Formation ◽  
Malignant Tumours ◽  
Iodonium Salts ◽  
Boronic Ester ◽  
Iodonium Salt ◽  
Kras Protein

Abstract Background: Oncrasin-1 is a small molecule which was identified from a screen of KRAS mutant cancer cells and has shown specificity for KRAS mutant cell killing. We aimed to develop a radiolabelled form of Oncrasin-1 to enable in-vivo imaging of mutant KRAS expression in malignant tumours. This work outlines the synthesis of 3 fluorinated derivatives and development of iodonium salt and boronic ester precursors for radiolabelling with the 18F isotope. Results: In our hands, synthesis of iodonium salts were not easily accessible due to the 3-carbaldehyde indole structure being preferentially oxidized by conditions required for iodonium salt formation, rather than benzyl iodide. Synthesis and radiolabelling of boronic acid pinacol ester precursors were successful, with the products being obtained in yields of 10.76% ± 0.96% (n=5), 14.7% ±8.58% (n=3) and 14.92% ±3.9% (n=3) for 18F KAM001, 18F KAM002 and 18F KAM003 respectively, with radiochemical purity of greater than 99%.Conclusions: The successful synthesis of these tracers has been undertaken utilizing boronic ester radio-fluorination methods and will allow for investigation of Oncrasin based molecules as potential diagnostics for cancers expressing mutant KRAS protein.

scholarly journals Guest Inclusion Crystal structures of Macrocyclic Boronic Esters

2014 ◽  
Vol 70 (a1) ◽  
pp. C677-C677
Author(s):  
Ryosuke Toyoshima ◽  
Kotaro Fujii ◽  
Kohei Johmoto ◽  
Hidehiro Uekusa ◽  
Yuji Kikuchi ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Boronic Acid ◽  
Guest Molecule ◽  
Covalent Bond ◽  
Macrocyclic Compound ◽  
Channel Structure ◽  
Monoclinic System ◽  
One Dimensional ◽  
Boronic Ester ◽  
Boronic Esters

Macrocyclic compound has been attracting increasing attention because of their application for guest absorption and storage, guest selectivity, and reaction environment, which would utilize void space in the compound. Recently, such macrocyclic compound, boronic esters, has found to be formed as dynamic self-assembly of organic molecules through solvent dependent dynamic covalent bond formation between racemic polyol and planar 1,4-benzen(boronic acid)[1]. Thus, it is important to determine the crystal structure of the macrocyclic boronic esters with incorporated guest molecule to reveal the features of the compounds. In this study, structures of boronic ester of 1,4- naphthalene(boronic acid) (1) are presented and compared. The boronic ester with toluene guest molecule crystalized in monoclinic system, C2/c, Z=4, V=5099.7(6) Å3. As expected, toluene molecule was accommodated within a ring sandwiched by two naphthalene rings suggesting π-π interaction (ca. 3.6 Å separations). It is interesting that other structures of 1 with 1,4-dicyanobenzene, chloroform, and THF also have isomorphic structures to 1 with toluene. It clearly shows the guest inclusion ability of this boronic ester by weak intermolecular interactions. In the crystal structures, the boronic ester aligned along b-axis forming one-dimensional stacking with channel structure filled with guest molecules. Also, 1 with chloroform has a pseudo-polymorph phase (P21/c, V=5780.8(13) Å3) that has two additional chloroform molecules inside and outside of the ring; however, it also shows similar one-dimensional stacking structure with channel, implying this boronic ester has an easily stacking molecular shape. Although, the molecules have similar [2+2] ring structure, dihedral angle between two facing naphthalene rings is different in 1 with toluene, which is smaller as 14.10than 22 to 240in other structures. It may indicate a flexibility of the macrocyclic ring.

scholarly journals Boronic ester derivative-dependent activity of parthenolide analogues

2021 ◽  
Author(s):  
Xingjian Li ◽  
George Williams ◽  
Alex Quy ◽  
Yiming Zhao ◽  
Louise Male ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Biological Activity ◽  
Chronic Lymphocytic Leukaemia ◽  
Boronic Acid ◽  
Lymphocytic Leukaemia ◽  
Ester Derivative ◽  
Boronic Ester ◽  
Dependent Activity ◽  
Oxidation By Hydrogen Peroxide

Four parthenolide derived prodrugs, containing different boronic ester moieties, were synthesised, their drug-like properties were calculated and their activity against chronic lymphocytic leukaemia (CLL) MEC1 cells measured. Differences in the clogP, the propensity towards oxidation by hydrogen peroxide, the affinity of the associated diols to a model boronic acid and the biological activity against MEC1 cells were contrasted, and it was found that the propensity for oxidation correlated to biological activity.

Dynamic and Programmable DNA-Templated Boronic Ester Formation

2011 ◽  
Vol 50 (18) ◽  
pp. 4193-4196 ◽  
Author(s):  
Anthony R. Martin ◽  
Ivan Barvik ◽  
Delphine Luvino ◽  
Michael Smietana ◽  
Jean-Jacques Vasseur
Keyword(s):  
Boronic Ester ◽  
Ester Formation

scholarly journals Interdependent Dynamic Nitroaldol and Boronic Ester Reactions for Complex Dynamers of Different Topologies

2021 ◽  
Author(s):  
Antanas Karalius ◽  
Yunchuan Qi ◽  
Mubarak Ayinla ◽  
Zoltan Szabo ◽  
Olof Ramstrom
Keyword(s):  
Dynamic Systems ◽  
Main Chain ◽  
Building Blocks ◽  
Boronic Acids ◽  
Complex Dynamic ◽  
Complex Dynamic Systems ◽  
Boronic Ester ◽  
Ester Formation ◽  
Nitroaldol Reaction ◽  
Hydrolysis Of

Complex dynamic systems displaying interdependency between nitroaldol and boronic ester reactions have been demonstrated. Nitroalkane-1,3-diols, generated by the nitroaldol reaction, were susceptible to ester formation with different boronic acids in aprotic solvents, whereas hydrolysis of the esters occurred in the presence of water. The boronic ester formation led to significant stabilization of the nitroaldol adducts under basic conditions. The use of bifunctional building blocks was furthermore established, allowing for main chain nitroaldol-boronate dynamers as well as complex network dynamers with distinct topologies. The shape and rigidity of the resulting dynamers showed an apparent dependency on the configuration of the boronic acids.

Improved δ-valerolactam templates for the assembly of Aβ-miniamyloids by boronic ester formation

2016 ◽  
Vol 14 (22) ◽  
pp. 5032-5048 ◽  
Author(s):  
André Wuttke ◽  
Sebastian Nils Fischer ◽  
Annika Nebel ◽  
Michael Marsch ◽  
Armin Geyer
Keyword(s):  
Boronic Ester ◽  
Ester Formation ◽  
Amyloidogenic Peptides

Numerically defined oligomers of amyloidogenic peptides were obtained by boronic ester formation with synthetic polyol templates.

scholarly journals Automated synthesis of 18F radiolabelled indole containing Oncrasin-like molecules; a comparison of iodonium salts and boronic ester chemistry

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Alexander F. McDonald ◽  
Yit Wooi Goh ◽  
Jonathan M. White ◽  
Andrew M. Scott ◽  
Uwe Ackermann
Keyword(s):  
Boronic Acid ◽  
Radiochemical Purity ◽  
Mutant Cell ◽  
Salt Formation ◽  
Malignant Tumours ◽  
Iodonium Salts ◽  
Boronic Ester ◽  
Iodonium Salt ◽  
Kras Protein

Abstract Background Oncrasin-1 is a small molecule which was identified from a screen of KRAS mutant cancer cells and has shown specificity for KRAS mutant cell killing. We aimed to develop a radiolabelled form of Oncrasin-1 to enable in-vivo imaging of mutant KRAS expression in malignant tumours. This work outlines the synthesis of 3 fluorinated derivatives and development of iodonium salt and boronic ester precursors for radiolabelling with the 18F isotope. Results In our hands, synthesis of iodonium salts were not easily accessible due to the 3-carbaldehyde indole structure being preferentially oxidized by conditions required for iodonium salt formation, rather than benzyl iodide. Synthesis and radiolabelling of boronic acid pinacol ester precursors were successful, with the products being obtained in yields of 10.76% ± 0.96% (n = 5), 14.7% ±8.58% (n = 3) and 14.92% ±3.9% (n = 3) for 18F KAM001, 18F KAM002 and 18F KAM003 respectively, with radiochemical purity of greater than 99%. Conclusions The successful synthesis of these tracers has been undertaken utilizing boronic ester radio-fluorination methods and will allow for investigation of Oncrasin based molecules as potential diagnostics for cancers expressing mutant KRAS protein.

scholarly journals Boronic ester derivative-dependent activity of parthenolide analogues

2021 ◽  
Author(s):  
Xingjian Li ◽  
George Williams ◽  
Alex Quy ◽  
Yiming Zhao ◽  
Louise Male ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Biological Activity ◽  
Chronic Lymphocytic Leukaemia ◽  
Boronic Acid ◽  
Lymphocytic Leukaemia ◽  
Ester Derivative ◽  
Boronic Ester ◽  
Dependent Activity ◽  
Oxidation By Hydrogen Peroxide

Four parthenolide derived prodrugs, containing different boronic ester moieties, were synthesised, their drug-like properties were calculated and their activity against chronic lymphocytic leukaemia (CLL) MEC1 cells measured. Differences in the clogP, the propensity towards oxidation by hydrogen peroxide, the affinity of the associated diols to a model boronic acid and the biological activity against MEC1 cells were contrasted, and it was found that the propensity for oxidation correlated to biological activity.

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