7NBL

Solution structure of DNA:RNA hybrid containing a 2'-deoxy-2'2'-difluorodeoxycytidine (gemcitabine) modification

Summary for 7NBL

• Entry DOI: 10.2210/pdb7nbl/pdb
• Related: 7NBK
• NMR Information: BMRB: 34595
• Descriptor: DNA (5'-D(*CP*TP*AP*(FFC)P*AP*CP*GP*G)-3'), RNA (5'-R(*CP*CP*GP*UP*GP*UP*AP*G)-3') (2 entities in total)
• Functional Keywords: fluorine modification, modified dna, gemcitabine, dna-rna hybrid
• Biological source: synthetic construct; More
• Total number of polymer chains: 2
• Total formula weight: 4990.15

Authors

Cabrero, C.,Martin-Pintado, N.,Mazzini, S.,Gargallo, R.,Eritja, R.,Avino, A.,Gonzalez, C. (deposition date: 2021-01-27, release date: 2021-04-07, Last modification date: 2024-05-15)

Primary citation

Cabrero, C.,Martin-Pintado, N.,Mazzini, S.,Gargallo, R.,Eritja, R.,Avino, A.,Gonzalez, C.
Structural Effects of Incorporation of 2 -Deoxy-2 2 -difluorodeoxycytidine (Gemcitabine) in A- and B-form Duplexes.
Chemistry, 2021

PubMed Abstract: We report the structural effect of 2'-deoxy-2',2'-difluorocytidine (dFdC) insertions in the DNA strand of a DNA : RNA hybrid duplex and in a self-complementary DNA : DNA duplex. In both cases, the modification slightly destabilizes the duplex and provokes minor local distortions that are more pronounced in the case of the DNA : RNA hybrid. Analysis of the solution structures determined by NMR methods show that dFdC is an adaptable derivative that adopts North type sugar conformation when inserted in pure DNA, or a South sugar conformation in the context of DNA : RNA hybrids. In this latter context, South sugar pucker favors the formation of a 2'F⋅⋅H8 attractive interaction with a neighboring purine, which compensates the destabilizing effect of base pair distortions. These interactions share some features with pseudohydrogen bonds described previously in other nucleic acids structures with fluorine modified sugars.

PubMed: 33772916
DOI: 10.1002/chem.202100503

Experimental method

SOLUTION NMR