Luis A Marky - Academia.edu (original) (raw)

Papers by Luis A Marky

Research paper thumbnail of B-DNA with 7-deaza-dG modification

Research paper thumbnail of X-ray structure of 7-deaza-dG and Z3dU modified duplex CGCGAATXCZCG

Research paper thumbnail of Handbook of Chemical Biology of Nucleic Acids

Handbook of Chemical Biology of Nucleic Acids

Research paper thumbnail of Thermodynamics for the Interaction of PEG-PLL Copolymers with DNA

Biophysical Journal, 2015

Research paper thumbnail of Unfolding and Binding Thermodynamics of the PREQ1 DNA Analog

The PreQ1 riboswitch is a subset of riboswitches found mainly in eubacteria. It plays an essentia... more The PreQ1 riboswitch is a subset of riboswitches found mainly in eubacteria. It plays an essential role in the biosynthesis of preQ1, a precursor to queuosine (Q). Q is a hypermodified guanine nucleotide that is universally found at the wobble position of certain tRNAs. PreQ1 forms a pseudoknot structure upon binding to preQ1. We use a combination of temperature-dependent UV spectroscopy and differential scanning calorimetry (DSC) to determine the unfolding thermodynamics of a DNA analog (PREQ1) and its control hairpin at two different salt concentrations, 16 mM and 116 mM Na+. Furthermore, we use DSC and fluorescence spectroscopy techniques to determine binding affinities, Kb, for the interaction of preq1 ligand with these DNA analogs. Both oligonucleotides unfold with TMs independent of strand concentration, indicating the formation of hairpin structures. The unfavorable unfolding free energy terms resulted from the typical compensation of an unfavorable enthalpy contributions (disruption of base-pair stacks) and favorable entropy contributions (release of ions and water molecules). The ligand preQ1 yielded a Kb of 5.7 x 105. Supported by NSF Grant (MCB-1912587).https://digitalcommons.unmc.edu/surp2021/1059/thumbnail.jp

Research paper thumbnail of The Inclusion of a GCAA Tetraloop Affects the Unfolding Thermodynamics of Intramolecular DNA Structures

Biophysical Journal, 2020

Research paper thumbnail of Thermodynamic investigation of the interaction of polycations with DNA

Research paper thumbnail of Energetics, Ion, and Water Binding of the Unfolding of AA/UU Base Pair Stacks and UAU/UAU Base Triplet Stacks in RNA

The Journal of Physical Chemistry B, 2018

Research paper thumbnail of Melting behavior of pseudoknots containing adjacent GC and AT rich domains

Biochemical Compounds, 2017

Research paper thumbnail of A Comparative Investigation of the Stability of DNA and RNA Pseudoknots

Biophysical Journal, 2016

Research paper thumbnail of Application of Modern Ultrasonic Velocity-Measurements for the Direct Investigation of the Hydration Changes in Dna-Ligand Interactions

Research paper thumbnail of Folding of Bent Oligodeoxynucleotide Duplexes: Energetics, Ion Binding, and Hydration

ACS Symposium Series, 2004

... interaction with the minor groove ligand netropsin; ii) the covalent placement of a benzopyre... more ... interaction with the minor groove ligand netropsin; ii) the covalent placement of a benzopyrene derivative into duplex DNA; iii) the covalent placement of cisplatin into a decamer duplex; and iv) the inclusion of aminopropyl cationic chains into the Dickerson-Drew dodecamer. ...

Research paper thumbnail of Rabankyrin-5 Interacts with EHD1 and Vps26 to Regulate Endocytic Trafficking and Retromer Function

Research paper thumbnail of Unfolding Thermodynamics of Intramolecular G-Quadruplexes: Base Sequence Contributions of the Loops †

The Journal of Physical Chemistry B, 2009

Research paper thumbnail of Unfolding Thermodynamics of DNA Pyrimidine Triplexes with Different Molecularities

The Journal of Physical Chemistry B, 2008

Nucleic acid oligonucleotides (ODNs), as drugs, present an exquisite selectivity and affinity tha... more Nucleic acid oligonucleotides (ODNs), as drugs, present an exquisite selectivity and affinity that can be used in antigene and antisense strategies for the control of gene expression. In this work we try to answer the following question: How does the molecularity of a DNA triplex affect its overall stability and melting behavior? To this end, we used a combination of temperature-dependent UV spectroscopy and calorimetric (differential scanning calorimetry) techniques to investigate the melting behavior of DNA triplexes with a similar helical stem, TC+TC+TC+T/AGAGAGA/TCTCTCT, but formed with different strand molecularity. We determined standard thermodynamic profiles and the differential binding of protons and counterions accompanying their unfolding. The formation of a triplex is accompanied by a favorable free energy term, resulting from the typical compensation of favorable enthalpy-unfavorable entropy contributions, i.e., the folding of a particular triplex is enthalpy driven. The magnitude of the favorable enthalpy contributions corresponds to the number and strength of the base-triplet stacks formed, which are helped by stacking contributions due to the incorporation of dangling ends or loops. Triplex stability is in the following order: monomolecular > bimolecular > trimolecular; this is explained in terms of additional stacking contributions due to the inclusion of loops. As expected, acidic pH stabilized all triplexes by allowing protonation of the cytosines in the third strand; however, the percentage of protonation increases as the molecularity decreases. The results help to choose adequate solution conditions for the study of triplexes containing different ratios of CGC+ and TAT base triplets and to aid in the design of oligonucleotide sequences as targeting reagents that could effectively react with mRNA sequences involved in human diseases, thereby increasing the feasibility of using the antisense strategy for therapeutic purposes.

Research paper thumbnail of Hydration Effects Accompanying the Substitution of Counterions in the Ionic Atmosphere of Poly(rA)·Poly(rU) and Poly(rA)·2Poly(rU) Helices

Journal of the American Chemical Society, 1996

The physical properties of nucleic acid helices strongly depend on their interaction with counter... more The physical properties of nucleic acid helices strongly depend on their interaction with counterions and water. Of special interest is the structure of their ionic atmosphere which is closely related to its overall hydration because the distances between counterions and the ...

Research paper thumbnail of Mg2+ recognizes the sequence of DNA through its hydration shell

Journal of the American Chemical Society, 1994

... Chem. SOC. 1994,116, 9423-9429 9423 Mg2+ Recognizes the Sequence of DNA through Its Hydration... more ... Chem. SOC. 1994,116, 9423-9429 9423 Mg2+ Recognizes the Sequence of DNA through Its Hydration Shell Vitaly A. Buckin,t BI Kankiya,* Dionisios Rentzeperis,lJ and Luis A. Marky'vs ... 2A, Chapter 6, pp 351-462. (38) Pavlov, M. Yu.; Fedorov, B. A. Biofizika 1983, 28, 931. ...

Research paper thumbnail of Shape-Selective Recognition of a Model Okazaki Fragment By Geometrically-Constrained Bis-Distamycins

Journal of Biomolecular Structure and Dynamics, 1999

Okazaki fragments represent interesting targets for the design of anticancer drugs because of the... more Okazaki fragments represent interesting targets for the design of anticancer drugs because of their selective occurrence during DNA replication, a process often elevated in aggressive malignancies. Structural studies have indicated a bend occurs in the helical axis at the junction region (JR) that joins the DNA duplex region (DDR) and the RNA-DNA hybrid duplex region (HDR) of model Okazaki fragments. To identify a structural motif that provides a shape complementary to the Okazaki fragment minor groove, we have investigated the binding of geometrically-constrained bis-distamycins to a model Okazaki fragment, [OKA], with a sequence derived from the genome of simian virus 40 (SV40). Both the JR and the DDR of [OKA] contain consecutive A/T base pairs that could accommodate distamycin binding. Of the six bis-distamycins selected for analysis, the two with a para configuration of the distamycins on the benzene or pyridine scaffold bound [OKA] tightly (Kd approximately 10(-6) M from gel-shift assays; Kd approximately 10(-8) M from deltaT(M)) while the four with a meta orientation did not bind. The two mono-distamycins studied also did not bind [OKA]. Molecular modeling of the complex between the para bis-distamycin MT-9 and [OKA] revealed MT-9 adopted an S- shape complementary to the minor groove of the model Okazaki fragment.

Research paper thumbnail of Energetic and Conformational Contributions to the Stability of Okazaki Fragments †

Research paper thumbnail of Melting Behavior of a DNA Four-way Junction Using Spectroscopic and Calorimetric Techniques

Journal of the American Chemical Society

Intramolecular four-way junctions are structures present during homologous recombination, repair ... more Intramolecular four-way junctions are structures present during homologous recombination, repair of double stranded DNA breaks, and integron recombination. Because of the wide range of biological processes four-way junctions are involved in, understanding how and under what conditions these structures form is critical. In this work, we used a combination of spectroscopic and calorimetric techniques to present a complete thermodynamic description of the unfolding of a DNA four-way junction (FWJ) and its appropriate control stem-loop motifs (Dumbbell, GAAATT-Hp, CTATC-Hp, GTGC-Hp, and GCGC-Hp). The overall results show that the four-way junction increases the cooperative unfolding of its stems, although the reason for this is unclear, as the arms do not unfold as coaxial stacks, and thus its melting behavior cannot be accurately described by its control molecules. This is in contrast to what has been seen for two- and three-way junctions. In addition, the lack of base stacking and the ΔHvH/ΔHcal ratio seen at low salt indicate the four-way junction exists as a mixture of conformations, one of which is most likely the open-X structure which has unpaired bases at the junction. This was confirmed by single value decomposition of CD and UV spectra. This indicates that at low salt there is a third spectroscopically distinct species, while at higher salt there are only two species, folded and unfolded. Based on the enthalpy, Δnion, and ΔnW, the dominant folded structure at high salt is most likely the antiparallel stacked-X structure.

Research paper thumbnail of B-DNA with 7-deaza-dG modification

Research paper thumbnail of X-ray structure of 7-deaza-dG and Z3dU modified duplex CGCGAATXCZCG

Research paper thumbnail of Handbook of Chemical Biology of Nucleic Acids

Handbook of Chemical Biology of Nucleic Acids

Research paper thumbnail of Thermodynamics for the Interaction of PEG-PLL Copolymers with DNA

Biophysical Journal, 2015

Research paper thumbnail of Unfolding and Binding Thermodynamics of the PREQ1 DNA Analog

The PreQ1 riboswitch is a subset of riboswitches found mainly in eubacteria. It plays an essentia... more The PreQ1 riboswitch is a subset of riboswitches found mainly in eubacteria. It plays an essential role in the biosynthesis of preQ1, a precursor to queuosine (Q). Q is a hypermodified guanine nucleotide that is universally found at the wobble position of certain tRNAs. PreQ1 forms a pseudoknot structure upon binding to preQ1. We use a combination of temperature-dependent UV spectroscopy and differential scanning calorimetry (DSC) to determine the unfolding thermodynamics of a DNA analog (PREQ1) and its control hairpin at two different salt concentrations, 16 mM and 116 mM Na+. Furthermore, we use DSC and fluorescence spectroscopy techniques to determine binding affinities, Kb, for the interaction of preq1 ligand with these DNA analogs. Both oligonucleotides unfold with TMs independent of strand concentration, indicating the formation of hairpin structures. The unfavorable unfolding free energy terms resulted from the typical compensation of an unfavorable enthalpy contributions (disruption of base-pair stacks) and favorable entropy contributions (release of ions and water molecules). The ligand preQ1 yielded a Kb of 5.7 x 105. Supported by NSF Grant (MCB-1912587).https://digitalcommons.unmc.edu/surp2021/1059/thumbnail.jp

Research paper thumbnail of The Inclusion of a GCAA Tetraloop Affects the Unfolding Thermodynamics of Intramolecular DNA Structures

Biophysical Journal, 2020

Research paper thumbnail of Thermodynamic investigation of the interaction of polycations with DNA

Research paper thumbnail of Energetics, Ion, and Water Binding of the Unfolding of AA/UU Base Pair Stacks and UAU/UAU Base Triplet Stacks in RNA

The Journal of Physical Chemistry B, 2018

Research paper thumbnail of Melting behavior of pseudoknots containing adjacent GC and AT rich domains

Biochemical Compounds, 2017

Research paper thumbnail of A Comparative Investigation of the Stability of DNA and RNA Pseudoknots

Biophysical Journal, 2016

Research paper thumbnail of Application of Modern Ultrasonic Velocity-Measurements for the Direct Investigation of the Hydration Changes in Dna-Ligand Interactions

Research paper thumbnail of Folding of Bent Oligodeoxynucleotide Duplexes: Energetics, Ion Binding, and Hydration

ACS Symposium Series, 2004

... interaction with the minor groove ligand netropsin; ii) the covalent placement of a benzopyre... more ... interaction with the minor groove ligand netropsin; ii) the covalent placement of a benzopyrene derivative into duplex DNA; iii) the covalent placement of cisplatin into a decamer duplex; and iv) the inclusion of aminopropyl cationic chains into the Dickerson-Drew dodecamer. ...

Research paper thumbnail of Rabankyrin-5 Interacts with EHD1 and Vps26 to Regulate Endocytic Trafficking and Retromer Function

Research paper thumbnail of Unfolding Thermodynamics of Intramolecular G-Quadruplexes: Base Sequence Contributions of the Loops †

The Journal of Physical Chemistry B, 2009

Research paper thumbnail of Unfolding Thermodynamics of DNA Pyrimidine Triplexes with Different Molecularities

The Journal of Physical Chemistry B, 2008

Nucleic acid oligonucleotides (ODNs), as drugs, present an exquisite selectivity and affinity tha... more Nucleic acid oligonucleotides (ODNs), as drugs, present an exquisite selectivity and affinity that can be used in antigene and antisense strategies for the control of gene expression. In this work we try to answer the following question: How does the molecularity of a DNA triplex affect its overall stability and melting behavior? To this end, we used a combination of temperature-dependent UV spectroscopy and calorimetric (differential scanning calorimetry) techniques to investigate the melting behavior of DNA triplexes with a similar helical stem, TC+TC+TC+T/AGAGAGA/TCTCTCT, but formed with different strand molecularity. We determined standard thermodynamic profiles and the differential binding of protons and counterions accompanying their unfolding. The formation of a triplex is accompanied by a favorable free energy term, resulting from the typical compensation of favorable enthalpy-unfavorable entropy contributions, i.e., the folding of a particular triplex is enthalpy driven. The magnitude of the favorable enthalpy contributions corresponds to the number and strength of the base-triplet stacks formed, which are helped by stacking contributions due to the incorporation of dangling ends or loops. Triplex stability is in the following order: monomolecular > bimolecular > trimolecular; this is explained in terms of additional stacking contributions due to the inclusion of loops. As expected, acidic pH stabilized all triplexes by allowing protonation of the cytosines in the third strand; however, the percentage of protonation increases as the molecularity decreases. The results help to choose adequate solution conditions for the study of triplexes containing different ratios of CGC+ and TAT base triplets and to aid in the design of oligonucleotide sequences as targeting reagents that could effectively react with mRNA sequences involved in human diseases, thereby increasing the feasibility of using the antisense strategy for therapeutic purposes.

Research paper thumbnail of Hydration Effects Accompanying the Substitution of Counterions in the Ionic Atmosphere of Poly(rA)·Poly(rU) and Poly(rA)·2Poly(rU) Helices

Journal of the American Chemical Society, 1996

The physical properties of nucleic acid helices strongly depend on their interaction with counter... more The physical properties of nucleic acid helices strongly depend on their interaction with counterions and water. Of special interest is the structure of their ionic atmosphere which is closely related to its overall hydration because the distances between counterions and the ...

Research paper thumbnail of Mg2+ recognizes the sequence of DNA through its hydration shell

Journal of the American Chemical Society, 1994

... Chem. SOC. 1994,116, 9423-9429 9423 Mg2+ Recognizes the Sequence of DNA through Its Hydration... more ... Chem. SOC. 1994,116, 9423-9429 9423 Mg2+ Recognizes the Sequence of DNA through Its Hydration Shell Vitaly A. Buckin,t BI Kankiya,* Dionisios Rentzeperis,lJ and Luis A. Marky'vs ... 2A, Chapter 6, pp 351-462. (38) Pavlov, M. Yu.; Fedorov, B. A. Biofizika 1983, 28, 931. ...

Research paper thumbnail of Shape-Selective Recognition of a Model Okazaki Fragment By Geometrically-Constrained Bis-Distamycins

Journal of Biomolecular Structure and Dynamics, 1999

Okazaki fragments represent interesting targets for the design of anticancer drugs because of the... more Okazaki fragments represent interesting targets for the design of anticancer drugs because of their selective occurrence during DNA replication, a process often elevated in aggressive malignancies. Structural studies have indicated a bend occurs in the helical axis at the junction region (JR) that joins the DNA duplex region (DDR) and the RNA-DNA hybrid duplex region (HDR) of model Okazaki fragments. To identify a structural motif that provides a shape complementary to the Okazaki fragment minor groove, we have investigated the binding of geometrically-constrained bis-distamycins to a model Okazaki fragment, [OKA], with a sequence derived from the genome of simian virus 40 (SV40). Both the JR and the DDR of [OKA] contain consecutive A/T base pairs that could accommodate distamycin binding. Of the six bis-distamycins selected for analysis, the two with a para configuration of the distamycins on the benzene or pyridine scaffold bound [OKA] tightly (Kd approximately 10(-6) M from gel-shift assays; Kd approximately 10(-8) M from deltaT(M)) while the four with a meta orientation did not bind. The two mono-distamycins studied also did not bind [OKA]. Molecular modeling of the complex between the para bis-distamycin MT-9 and [OKA] revealed MT-9 adopted an S- shape complementary to the minor groove of the model Okazaki fragment.

Research paper thumbnail of Energetic and Conformational Contributions to the Stability of Okazaki Fragments †

Research paper thumbnail of Melting Behavior of a DNA Four-way Junction Using Spectroscopic and Calorimetric Techniques

Journal of the American Chemical Society

Intramolecular four-way junctions are structures present during homologous recombination, repair ... more Intramolecular four-way junctions are structures present during homologous recombination, repair of double stranded DNA breaks, and integron recombination. Because of the wide range of biological processes four-way junctions are involved in, understanding how and under what conditions these structures form is critical. In this work, we used a combination of spectroscopic and calorimetric techniques to present a complete thermodynamic description of the unfolding of a DNA four-way junction (FWJ) and its appropriate control stem-loop motifs (Dumbbell, GAAATT-Hp, CTATC-Hp, GTGC-Hp, and GCGC-Hp). The overall results show that the four-way junction increases the cooperative unfolding of its stems, although the reason for this is unclear, as the arms do not unfold as coaxial stacks, and thus its melting behavior cannot be accurately described by its control molecules. This is in contrast to what has been seen for two- and three-way junctions. In addition, the lack of base stacking and the ΔHvH/ΔHcal ratio seen at low salt indicate the four-way junction exists as a mixture of conformations, one of which is most likely the open-X structure which has unpaired bases at the junction. This was confirmed by single value decomposition of CD and UV spectra. This indicates that at low salt there is a third spectroscopically distinct species, while at higher salt there are only two species, folded and unfolded. Based on the enthalpy, Δnion, and ΔnW, the dominant folded structure at high salt is most likely the antiparallel stacked-X structure.