Truncated S-MGBs: towards a parasite-specific and low aggregation chemotype

RSC Medicinal Chemistry ◽

10.1039/d1md00110h ◽

2021 ◽

Author(s):

Daniel P. Brooke ◽

Leah M. C. McGee ◽

Federica Giordani ◽

Jasmine M. Cross ◽

Abedawn I. Khalaf ◽

...

Keyword(s):

Natural Product ◽

Pyrrole Ring ◽

Minor Groove ◽

Design And Synthesis ◽

Minor Groove Binders ◽

Groove Binders

This paper describes the design and synthesis of Strathclyde minor groove binders (S-MGBs) that have been truncated by the removal of a pyrrole ring in order to mimic the structure of the natural product, disgocidine.

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Application of Cu(I)-catalyzed azide–alkyne cycloaddition for the design and synthesis of sequence specific probes targeting double-stranded DNA

Beilstein Journal of Organic Chemistry ◽

10.3762/bjoc.12.128 ◽

2016 ◽

Vol 12 ◽

pp. 1348-1360 ◽

Cited By ~ 4

Author(s):

Svetlana V Vasilyeva ◽

Vyacheslav V Filichev ◽

Alexandre S Boutorine

Keyword(s):

Minor Groove ◽

Binding Parameters ◽

Design And Synthesis ◽

Minor Groove Binders ◽

Double Stranded Dna ◽

Triple Helices ◽

Gel Shift ◽

Groove Binders

Efficient protocols based on Cu(I)-catalyzed azide–alkyne cycloaddition were developed for the synthesis of conjugates of pyrrole–imidazole polyamide minor groove binders (MGB) with fluorophores and with triplex-forming oligonucleotides (TFOs). Diverse bifunctional linkers were synthesized and used for the insertion of terminal azides or alkynes into TFOs and MGBs. The formation of stable triple helices by TFO-MGB conjugates was evaluated by gel-shift experiments. The presence of MGB in these conjugates did not affect the binding parameters (affinity and triplex stability) of the parent TFOs.

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Four pyrrole derivatives used as building blocks in the synthesis of minor-groove binders

Acta Crystallographica Section E Crystallographic Communications ◽

10.1107/s2056989017001177 ◽

2017 ◽

Vol 73 (2) ◽

pp. 254-259 ◽

Cited By ~ 2

Author(s):

Alan R. Kennedy ◽

Abedawn I. Khalaf ◽

Fraser J. Scott ◽

Colin J. Suckling

Keyword(s):

Hydrogen Bonds ◽

Pyrrole Ring ◽

Building Blocks ◽

Minor Groove ◽

The Other ◽

Pyrrole Derivatives ◽

Dna Minor Groove ◽

Minor Groove Binders ◽

Modified Dna ◽

Groove Binders

The title nitropyrrole-based compounds, C7H8N2O4, (I) (ethyl 4-nitro-1H-pyrrole-2-carboxylate), its derivative C12H14N2O4, (II) [ethyl 4-nitro-1-(4-pentynyl)-1H-pyrrole-2-carboxylate], C15H26N4O3, (III) {N-[3-(dimethyamino)propyl]-1-isopentyl-4-nitro-1H-pyrrole-2-carboxamide}, and C20H27N9O5, (IV) {1-(3-azidopropyl)-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamido)-N-[2-(morpholin-4-yl)ethyl]-1H-pyrrole-2-carboxamide}, are intermediates used in the synthesis of modified DNA minor-groove binders. In all four compounds, the nitro groups lie in the plane of the pyrrole ring. In compounds (I) and (II), the ester groups also lie in the plane of the pyrrole ring. In compound (III), both of the other substituents lie out of the plane of the pyrrole ring. In the case of compound (IV), the coplanarity extends to the second pyrrole ring and through both amide groups. In the crystals of all four compounds, layer-like structures are formed,viaa combination of N—H...O and C—H...O hydrogen bonds for (I), (III) and (IV), but by only C—H...O hydrogen bonds for (II).

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