Conformational constraints of cyclopentane peptide nucleic acids facilitate tunable binding to DNA
Conformational constraints of cyclopentane peptide nucleic acids facilitate tunable binding to DNA
Abstract We report a series of synthetic, nucleic acid mimics with highly customizable thermodynamic binding to DNA. Incorporation of helix-promoting cyclopentanes into peptide nucleic acids (PNAs) increases the melting temperatures (Tm) of PNA+DNA duplexes by approximately +5°C per cyclopentane. Sequential addition of cyclopentanes allows the Tm of PNA + DNA duplexes to be systematically fine-tuned from +5 to +50°C compared with the unmodified PNA. Containing only nine nucleobases and an equal number of cyclopentanes, cpPNA-9 binds to complementary DNA with a Tm around 90°C. Additional experiments reveal that the cpPNA-9 sequence specifically binds to DNA duplexes containing its complementary sequence and functions as a PCR clamp. An X-ray crystal structure of the cpPNA-9–DNA duplex revealed that cyclopentanes likely induce a right-handed helix in the PNA with conformations that promote DNA binding.
- National Cancer Institute United States
- National Institutes of Health United States
- National Institute of Health Pakistan
- Department of Health and Human Services United States
- Austin Health & Human Services Department United States
Models, Molecular, Peptide Nucleic Acids, Circular Dichroism, Cyclopentanes, DNA, Calorimetry, Crystallography, X-Ray, Nucleic Acid Denaturation, Real-Time Polymerase Chain Reaction, Nucleic Acid Conformation, Thermodynamics, Transition Temperature, Spectrophotometry, Ultraviolet
Models, Molecular, Peptide Nucleic Acids, Circular Dichroism, Cyclopentanes, DNA, Calorimetry, Crystallography, X-Ray, Nucleic Acid Denaturation, Real-Time Polymerase Chain Reaction, Nucleic Acid Conformation, Thermodynamics, Transition Temperature, Spectrophotometry, Ultraviolet
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