Wade Grabow - Academia.edu (original) (raw)

Papers by Wade Grabow

Nucleic Acids Research, May 2, 2019

Naturally occurring RNAs are known to exhibit a high degree of modularity, whereby specific struc... more Naturally occurring RNAs are known to exhibit a high degree of modularity, whereby specific structural modules (or motifs) can be mixed and matched to create new molecular architectures. The modular nature of RNA also affords researchers the ability to characterize individual structural elements in controlled synthetic contexts in order to gain new and critical insights into their particular structural features and overall performance. Here, we characterized the binding affinity of a unique loop-receptor interaction found in the tetrahydrofolate (THF) riboswitch using rationally designed self-assembling tectoRNAs. Our work suggests that the THF loopreceptor interaction has been fine-tuned for its particular role as a riboswitch component. We also demonstrate that the thermodynamic stability of this interaction can be modulated by the presence of folinic acid, which induces a local structural change at the level of the loop-receptor. This corroborates the existence of a THF binding site within this tertiary module and paves the way for its potential use as a THF responsive module for RNA nanotechnology and synthetic biology.

Nature Materials, Mar 22, 2012

Self-assembled microsponges of hairpin RNA polymers achieve, with one thousand times lower concen... more Self-assembled microsponges of hairpin RNA polymers achieve, with one thousand times lower concentration, the same degree of gene silencing in tumour-carrying mice as conventional nanoparticle-based siRNA delivery vehicles.

Photodynamic therapy (PDT) has been investigated over the past three decades and is currently an ... more Photodynamic therapy (PDT) has been investigated over the past three decades and is currently an approved therapeutic modality for skin cancer, the treatment of superficial bladder, early lung and advanced esophageal cancers, and age-related macular degeneration in a number of countries. In PDT, the absorption of light by a chromophore generates cytotoxic species such as reactive singlet oxygen, leading to irreversible destruction of the treated tissue. The measurement of the singlet oxygen quantum yield (φ ∆) is an important determinant used to evaluate the efficiency of new photodynamic therapy agents developed in the laboratory, to screen potential photosensitizers in aqueous media. The singlet oxygen quantum yield is a quantitative measurement of the efficiency in which photosensitizers are able to use energy, in the form of light, to convert oxygen in the ground state to the reactive species singlet oxygen, O 2 (1 ∆ g), useful in photodynamic therapy. Singlet oxygen quantum yields of photosensitizers differ when measured in different solvents. The majority of the existing φ ∆ values found in literature for various photosensitizers are documented with the sensitizers in organic solvents though values in aqueous media are more valuable for actual applications. Determination of accurate and precise φ ∆ values in aqueous solution is a much more difficult problem than in organic media. Problems in aqueous solution arise primarily from the physicochemical properties of O 2 (1 ∆ g) in water. Singlet oxygen has a iv much shorter lifetime in water than it does in organic solvents, causing challenges with respect to quantitative detection of O 2 (1 ∆ g). The ensuing pages are an attempt to explore the theory and document the procedures developed to provide the accurate measurement of O 2 (1 ∆ g) in aqueous media. Details of this experimental method and singlet oxygen quantum yield results of new compounds relative to established photosensitizers will be presented. v I dedicate this work to my beautiful and amazing wife Amy. None of this would have ever been possible without her understanding, patience, and encouragement. I thank God for this opportunity and experience, to include all that I have learned about myself and what is really important in life as a result of these last two years of determined work. vi ACKNOWLEDGMENTS This thesis would not have been possible without the help of a number of individuals. I would like to thank Dr. Kevin Belfield and his research group for all of the support that they provided throughout the last two years. Particularly, I would like to thank Katherine Schafer for all the times she went out of her way to help me. Lastly, I would like to thank my friends and family who helped me along the way. Thank you. vii

... 1993, 34, 6669-6671. (CH3 )4 NOSCF3 O O R = -CH 3 + Br OR NH O Br OR N O + HOSCF3 O O NO2 NO2... more ... 1993, 34, 6669-6671. (CH3 )4 NOSCF3 O O R = -CH 3 + Br OR NH O Br OR N O + HOSCF3 O O NO2 NO2 ... O NH N N OCH3 H3CO Cl NH2 + POLYCYCLIC MOLECULE 1 O NH N N OCH3 H3CO HN POLYCYCLIC MOLECULE 2 POLYCYCLIC MOLECULE 2 [H2] Page 8. 7 ...

... (Preprint) Scott T. Iacono, † Wade Grabow, ‡ Ashwani Vij, ‡ Dennis W. Smith, Jr., † and Josep... more ... (Preprint) Scott T. Iacono, † Wade Grabow, ‡ Ashwani Vij, ‡ Dennis W. Smith, Jr., † and Joseph M. Mabry* ,‡ ... (7) For recent examples of co-polymers, see: (a) Zheng, L.; Hong, S.; Cardoen, G.; Burgaz, E.; Gido, SP; Coughlin, EB Macromolecules 2004, 37, 8606. ...

Public reporting burden for this collection of information is estimated to average 1 hour per res... more Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information,

Biosystems, 2019

Biological information is most commonly thought of in terms of biology's Central Dogma where DNA ... more Biological information is most commonly thought of in terms of biology's Central Dogma where DNA is viewed as a linearized code used to synthesize proteins. Using DNA's chemical cousin, RNA, as a case study we consider how biological information operates outside the linear arrangement of its polymeric subunits. Much like individual pieces of a jigsaw puzzle, particular structures enable biomolecules to undergo precise molecular interactions with one another based on their respective shapes. By exploring the relationship between sequence and structure in RNA we argue that biological information finds its ultimate functional fulfillment in the threedimensional structural arrangement of its atoms. We show how recurrent structural RNA motifs-operating at the tertiary level of a molecule-provide robust building blocks for the formation of new structural configurations and thereby convey the information required for emergent biological functions. We posit that these same RNA structures, guided by their respective thermodynamic stabilities, experience selective pressure to maintain particular three-dimensional architectures over and above pressures to maintain a particular sequence of nucleotides. Ultimately, this framework for understanding the nature of biological information provides a useful paradigm for understanding its origins and how biological information can result from chaotic prebiotic conditions.

ACS Symposium Series, 2007

Public reporting burden for this collection of information is estimated to average 1 hour per res... more Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number.

The novel compound with the following nominal formulation (Cd, Zn) 2.5 Fe(P 2 O 7) 2 has been suc... more The novel compound with the following nominal formulation (Cd, Zn) 2.5 Fe(P 2 O 7) 2 has been successfully prepared by the solid state reaction and characterized by single-crystal X-ray diffraction. This phosphate crystallizes in the orthorhombic system with the C222 1 space group. Its crystal structure is formed by five types of cationic sites and by two unique (P 2 O 7) 4anionic groups with a staggered conformation. In the structure, three sites are fulfilled by Zn 2+ :(Zn(3), Zn(4)) and Fe(1) 3+ , the fourth site is localized in the Wyckoff position 4a (site symmetry 2. .) and is statically occupied by Cd 2+ : Zn 2+ with ratio 0.586(2) : 0.413(8). The last site, localized in 8c Wyckoff position (site symmetry 1) is also occupied by a mixture of the two cations Cd 2+ : Zn 2+ with occupancies of 0.444(6) : 0.555(4).Within this framework, the metallic polyhedra [MO n ] (n = 5 or 6) form corrugated layers stacked along the b-axis, and intercalated by P 2 O 7 groups.

Nucleic Acids Research, May 2, 2019

Naturally occurring RNAs are known to exhibit a high degree of modularity, whereby specific struc... more Naturally occurring RNAs are known to exhibit a high degree of modularity, whereby specific structural modules (or motifs) can be mixed and matched to create new molecular architectures. The modular nature of RNA also affords researchers the ability to characterize individual structural elements in controlled synthetic contexts in order to gain new and critical insights into their particular structural features and overall performance. Here, we characterized the binding affinity of a unique loop-receptor interaction found in the tetrahydrofolate (THF) riboswitch using rationally designed self-assembling tectoRNAs. Our work suggests that the THF loopreceptor interaction has been fine-tuned for its particular role as a riboswitch component. We also demonstrate that the thermodynamic stability of this interaction can be modulated by the presence of folinic acid, which induces a local structural change at the level of the loop-receptor. This corroborates the existence of a THF binding site within this tertiary module and paves the way for its potential use as a THF responsive module for RNA nanotechnology and synthetic biology.

Nature Materials, Mar 22, 2012

Self-assembled microsponges of hairpin RNA polymers achieve, with one thousand times lower concen... more Self-assembled microsponges of hairpin RNA polymers achieve, with one thousand times lower concentration, the same degree of gene silencing in tumour-carrying mice as conventional nanoparticle-based siRNA delivery vehicles.

Photodynamic therapy (PDT) has been investigated over the past three decades and is currently an ... more Photodynamic therapy (PDT) has been investigated over the past three decades and is currently an approved therapeutic modality for skin cancer, the treatment of superficial bladder, early lung and advanced esophageal cancers, and age-related macular degeneration in a number of countries. In PDT, the absorption of light by a chromophore generates cytotoxic species such as reactive singlet oxygen, leading to irreversible destruction of the treated tissue. The measurement of the singlet oxygen quantum yield (φ ∆) is an important determinant used to evaluate the efficiency of new photodynamic therapy agents developed in the laboratory, to screen potential photosensitizers in aqueous media. The singlet oxygen quantum yield is a quantitative measurement of the efficiency in which photosensitizers are able to use energy, in the form of light, to convert oxygen in the ground state to the reactive species singlet oxygen, O 2 (1 ∆ g), useful in photodynamic therapy. Singlet oxygen quantum yields of photosensitizers differ when measured in different solvents. The majority of the existing φ ∆ values found in literature for various photosensitizers are documented with the sensitizers in organic solvents though values in aqueous media are more valuable for actual applications. Determination of accurate and precise φ ∆ values in aqueous solution is a much more difficult problem than in organic media. Problems in aqueous solution arise primarily from the physicochemical properties of O 2 (1 ∆ g) in water. Singlet oxygen has a iv much shorter lifetime in water than it does in organic solvents, causing challenges with respect to quantitative detection of O 2 (1 ∆ g). The ensuing pages are an attempt to explore the theory and document the procedures developed to provide the accurate measurement of O 2 (1 ∆ g) in aqueous media. Details of this experimental method and singlet oxygen quantum yield results of new compounds relative to established photosensitizers will be presented. v I dedicate this work to my beautiful and amazing wife Amy. None of this would have ever been possible without her understanding, patience, and encouragement. I thank God for this opportunity and experience, to include all that I have learned about myself and what is really important in life as a result of these last two years of determined work. vi ACKNOWLEDGMENTS This thesis would not have been possible without the help of a number of individuals. I would like to thank Dr. Kevin Belfield and his research group for all of the support that they provided throughout the last two years. Particularly, I would like to thank Katherine Schafer for all the times she went out of her way to help me. Lastly, I would like to thank my friends and family who helped me along the way. Thank you. vii

... 1993, 34, 6669-6671. (CH3 )4 NOSCF3 O O R = -CH 3 + Br OR NH O Br OR N O + HOSCF3 O O NO2 NO2... more ... 1993, 34, 6669-6671. (CH3 )4 NOSCF3 O O R = -CH 3 + Br OR NH O Br OR N O + HOSCF3 O O NO2 NO2 ... O NH N N OCH3 H3CO Cl NH2 + POLYCYCLIC MOLECULE 1 O NH N N OCH3 H3CO HN POLYCYCLIC MOLECULE 2 POLYCYCLIC MOLECULE 2 [H2] Page 8. 7 ...

... (Preprint) Scott T. Iacono, † Wade Grabow, ‡ Ashwani Vij, ‡ Dennis W. Smith, Jr., † and Josep... more ... (Preprint) Scott T. Iacono, † Wade Grabow, ‡ Ashwani Vij, ‡ Dennis W. Smith, Jr., † and Joseph M. Mabry* ,‡ ... (7) For recent examples of co-polymers, see: (a) Zheng, L.; Hong, S.; Cardoen, G.; Burgaz, E.; Gido, SP; Coughlin, EB Macromolecules 2004, 37, 8606. ...

Public reporting burden for this collection of information is estimated to average 1 hour per res... more Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information,

Biosystems, 2019

Biological information is most commonly thought of in terms of biology's Central Dogma where DNA ... more Biological information is most commonly thought of in terms of biology's Central Dogma where DNA is viewed as a linearized code used to synthesize proteins. Using DNA's chemical cousin, RNA, as a case study we consider how biological information operates outside the linear arrangement of its polymeric subunits. Much like individual pieces of a jigsaw puzzle, particular structures enable biomolecules to undergo precise molecular interactions with one another based on their respective shapes. By exploring the relationship between sequence and structure in RNA we argue that biological information finds its ultimate functional fulfillment in the threedimensional structural arrangement of its atoms. We show how recurrent structural RNA motifs-operating at the tertiary level of a molecule-provide robust building blocks for the formation of new structural configurations and thereby convey the information required for emergent biological functions. We posit that these same RNA structures, guided by their respective thermodynamic stabilities, experience selective pressure to maintain particular three-dimensional architectures over and above pressures to maintain a particular sequence of nucleotides. Ultimately, this framework for understanding the nature of biological information provides a useful paradigm for understanding its origins and how biological information can result from chaotic prebiotic conditions.

ACS Symposium Series, 2007

Public reporting burden for this collection of information is estimated to average 1 hour per res... more Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number.

The novel compound with the following nominal formulation (Cd, Zn) 2.5 Fe(P 2 O 7) 2 has been suc... more The novel compound with the following nominal formulation (Cd, Zn) 2.5 Fe(P 2 O 7) 2 has been successfully prepared by the solid state reaction and characterized by single-crystal X-ray diffraction. This phosphate crystallizes in the orthorhombic system with the C222 1 space group. Its crystal structure is formed by five types of cationic sites and by two unique (P 2 O 7) 4anionic groups with a staggered conformation. In the structure, three sites are fulfilled by Zn 2+ :(Zn(3), Zn(4)) and Fe(1) 3+ , the fourth site is localized in the Wyckoff position 4a (site symmetry 2. .) and is statically occupied by Cd 2+ : Zn 2+ with ratio 0.586(2) : 0.413(8). The last site, localized in 8c Wyckoff position (site symmetry 1) is also occupied by a mixture of the two cations Cd 2+ : Zn 2+ with occupancies of 0.444(6) : 0.555(4).Within this framework, the metallic polyhedra [MO n ] (n = 5 or 6) form corrugated layers stacked along the b-axis, and intercalated by P 2 O 7 groups.