Customizable and Regioselective One-Pot N-H Functionalization of DNA Nucleobases to Create a Library of Nucleobase Derivatives for Biomedical Applications

authors	Rocha, DHA; Machado, CM; Sousa, V; Sousa, CFV; Silva, VLM; Silva, AMS; Borges, J; Mano, JF
nationality	International
journal	EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
author keywords	Biomedicine; Cell culture; Nucleobases; One-pot synthesis; Regioselectivity
keywords	MICHAEL ADDITION; NUCLEIC-ACIDS; ADENINE; PYRIMIDINE; THYMINE; URACIL; COMBINATION; ALKYLATION; EFFICIENT; POLYMERS
abstract	DNA is one of the most exciting biomolecules in nature for developing supramolecular biofunctional nanoarchitectures owing to the highly specific and selective interactions between complementary Watson-Crick base pairing. Herein, simple and one-pot synthetic procedures have been implemented for producing a library of DNA nucleobase derivatives endowed with reactive functional groups for bioconjugation and cross-linking strategies with other (bio)molecules. Purine and pyrimidine molecules have been regioselectively N-H functionalized either via N-alkylation, N-allylation, N-propargylation or Michael-type reactions and structurally characterized. The influence of the reaction conditions was assessed and discussed. The in vitro biocompatibility of the native and nucleobase derivatives was evaluated by culturing them with human fibroblasts, revealing their cytocompatibility. The library of nucleobase derivatives holds great promise for being coupled to different biomolecules, including biopolymeric materials, lipids, and peptides, thus potentially leading to modular supramolecular nanobiomaterials for biomedicine.
publisher	WILEY-V C H VERLAG GMBH
issn	1434-193X
isbn	1099-0690
year published	2021
volume	2021
issue	31
beginning page	4423
ending page	4433
digital object identifier (doi)	10.1002/ejoc.202100786
web of science category	11
subject category	Chemistry, Organic
unique article identifier	WOS:000688733800003