7UID

Thyclotides peptide nucleic acid in complex with DNA

Summary for 7UID

• Entry DOI: 10.2210/pdb7uid/pdb
• Descriptor: DNA (5'-D(*GP*AP*TP*GP*TP*GP*AP*TP*A)-3'), Thyclotide, ZINC ION, ... (5 entities in total)
• Functional Keywords: thyclotides, peptide nucleic acid, pna, peptide nucleic acid-dna complex, dna-peptide nucleic acid complex, dna/peptide nucleic acid
• Biological source: synthetic construct; More
• Total number of polymer chains: 4
• Total formula weight: 12114.43

Authors

Botos, I.,Appella, D.H. (deposition date: 2022-03-29, release date: 2023-04-05, Last modification date: 2025-07-02)

Primary citation

Zheng, H.,Clausse, V.,Amarasekara, H.,Mazur, S.J.,Botos, I.,Appella, D.H.
Variation of Tetrahydrofurans in Thyclotides Enhances Oligonucleotide Binding and Cellular Uptake of Peptide Nucleic Acids.
Jacs Au, 3:1952-1964, 2023

PubMed Abstract: Selective incorporation of conformational constraints into thyclotides can be used to modulate their binding to complementary oligonucleotides, increase polarity, and optimize uptake into HCT116 cells without assistance from moieties known to promote cell uptake. The X-ray structure and biophysical studies of a thyclotide-DNA duplex reveal that incorporation of tetrahydrofurans into an PNA backbone promotes a helical conformation that enhances binding to complementary DNA and RNA. Selective incorporation of tetrahydrofurans into the PNA backbone allows polarity to be increased incrementally so that uptake into HCT116 cells can be optimized. The enhanced binding, polarity, and cellular uptake properties of thyclotides were used to demonstrate effective inhibition of microRNA-21 in HCT116 cells.

PubMed: 37502163
DOI: 10.1021/jacsau.3c00198

Experimental method

X-RAY DIFFRACTION (2 Å)