Lincoln G. Scott

Lincoln G. Scott
Cassia, LLC

B.A., Ph.D.

About

37
Publications
2,906
Reads
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1,251
Citations
Introduction
Dr. Scott has broad interdisciplinary experience in both the biological as well as chemical sciences (3 decades). His research goals are to seamlessly integrate and leverage the physical and life sciences to advance basic science research and medicine.
Additional affiliations
October 2005 - present
Cassia, LLC
Cassia, LLC
Position
  • Founder & CSO
Description
  • CRO Specializing in the Green Chemo-Enzymatic Syntheses of Isotopically Labeled Primary and Secondary Metabolites (and Analogs) for Biomedical Research Applications
January 2001 - September 2005
The Scripps Research Institute
Position
  • Research Associate
Description
  • Structural Studies of RNA and RNA-Protein Complexes Involved in Post-Transcriptional Gene Regulation and Ribosome Biogenesis
January 1998 - December 2000
The Scripps Research Institute
Position
  • Research Associate
Description
  • Biochemical Studies of RNA and RNA-Protein Complexes Involved in Post-Transcriptional Gene Regulation and Ribosome Biogenesis
Education
January 2001 - September 2005
The Scripps Research Institute
Field of study
  • Biophysics
January 1998 - December 2000
The Scripps Research Institute
Field of study
  • Molecular Biology
August 1997 - December 1997
Massachusetts Institute of Technology
Field of study
  • Biocatalysis

Publications

Publications (37)
Chapter
Naturally occurring RNA lacks fluorine-19 (19F), thus, their specifically fluorinated counterparts are particularly well suited to noninvasively monitoring the dynamic conformational properties and ligand-binding interactions of the RNA. For nuclear magnetic resonance (NMR) spectroscopy, 19F-NMR of fluorine-substituted RNA provides an attractive, s...
Article
Active-site guanines that occupy similar positions have been proposed to serve as general base catalysts in hammerhead, hairpin, and glmS ribozymes, but no specific roles for these guanines have been demonstrated conclusively. Structural studies place G33(N1) of the glmS ribozyme of Bacillus anthracis within hydrogen-bonding distance of the 2'-OH n...
Article
Full-text available
LC/MS analysis of ribonucleosides is traditionally performed by reverse phase chromatography on silica based C18 type stationary phases using MS compatible buffers and methanol or acetonitrile gradients. Due to the hydrophilic and polar nature of nucleosides, down-scaling C18 analytical methods to a two-column nano-flow setup is inherently difficul...
Article
Full-text available
Understanding how self-cleaving ribozymes mediate catalysis is crucial in light of compelling evidence that human and bacterial gene expression can be regulated through RNA self-cleavage. The hairpin ribozyme catalyzes reversible phosphodiester bond cleavage through a mechanism that does not require divalent metal cations. Previous structural and b...
Article
The use of stable isotope labeling has revolutionized NMR studies of nucleic acids, and there is a need for methods of incorporation of specific isotope labels to facilitate specific NMR experiments and applications. Enzymatic synthesis offers an efficient and flexible means to synthesize nucleoside triphosphates from a variety of commercially avai...
Article
Full-text available
Active site guanines are critical for self-cleavage reactions of several ribozymes, but their precise functions in catalysis are unclear. To learn whether protonated or deprotonated forms of guanine predominate in the active site, microscopic pKa values were determined for ionization of 8-azaguanosine substituted for G8 in the active site of a full...
Article
A general method for isotopic labeling of the purine base moiety of nucleotides and RNA has been developed through biochemical pathway engineering in vitro. A synthetic scheme was designed and implemented utilizing recombinant enzymes from the pentose phosphate and de novo purine synthesis pathways, with regeneration of folate, aspartate, glutamine...
Article
This chapter reviews the methodologies for RNA structure determination by liquid-state nuclear magnetic resonance (NMR). The routine production of milligram quantities of isotopically labeled RNA remains critical to the success of NMR-based structure studies. The standard method for the preparation of isotopically labeled RNA for structural studies...
Article
Enzymatic synthesis methods for the fluorinated 5'-triphosphate analogues 5F-UTP and 5F-CTP have been developed to facilitate 19F-labeling of RNAs for biophysical studies. HIV-2 TAR RNAs were synthesized using these analogues by in vitro transcription reactions using T7 RNA polymerase. The uniform incorporation of 5F-U or 5F-C analogues into HIV-2...
Article
Simulation and experiment have been used to establish that significant artifacts can be generated in X-pulse CPMG relaxation dispersion experiments recorded on heteronuclear ABX spin-systems, such as 13Ci –13Cj –1H, where 13Ci and 13Cj are strongly coupled. A qualitative explanation of the origin of these artifacts is presented along with a simple...
Article
The fluorescent nucleotide analogue 8-azaguanosine-5'-triphosphate (8azaGTP) is prepared easily by in vitro enzymatic synthesis methods. 8azaGTP is an efficient substrate for T7 RNA polymerase and is incorporated specifically opposite cytosine in the transcription template, as expected for a nucleobase analogue with the same Watson-Crick hydrogen b...
Article
A new labeling strategy is presented that greatly facilitates the measurement of 2H spin relaxation rates in RNA molecules as a probe of pico- to nanosecond time scale dynamics. In this labeling scheme the sugar positions are uniformly 13C-labeled, with position 2' protonated and all other sites on the sugar deuterated. Pulse sequences are presente...
Article
Long-range scalar 5J(H1',F) couplings were observed in 5-fluoropyrimidine-substituted RNA. We developed a novel S3E-19F-alpha,beta-edited NOESY experiment for quantitation of these long-range scalar 5J(H1',F) couplings, where the J-couplings can be extracted from inspection of intraresidual (H1',H6) NOE cross-peaks. Quantum chemical calculations we...
Article
The Bacillus stearothermophilus ribosomal protein S15 (BS15) binds a purine-rich three-helix junction motif in the central domain of 16S ribosomal RNA (rRNA) as well as a translational operator located in the 5'-untranslated region (5'-UTR) of its cognate messenger RNA (mRNA). An in-frame fusion between the 5'-UTR of the BS15 gene and beta-galactos...
Article
Tertiary interactions are critical for proper RNA folding and ribozyme catalysis. RNA tertiary structure is often condensed through long-range helical packing interactions mediated by loop-receptor motifs. RNA structures displaying helical packing by loop-receptor interactions have been solved by X-ray crystallography, but not by NMR. Here, we repo...
Article
The production of isotopically labeled RNA remains critical to current NMR structural studies. One approach to obtain simple NMR spectra is to label with a nucleus that is not naturally occurring in RNA. Fluorine-19 can serve as a sensitive site-specific probe upon incorporation into RNA. Here we report the efficient in vitro enzymatic synthesis of...
Article
Full-text available
We report the fabrication of enthalpy arrays and their use to detect molecular interactions, including protein-ligand binding, enzymatic turnover, and mitochondrial respiration. Enthalpy arrays provide a universal assay methodology with no need for specific assay development such as fluorescent labeling or immobilization of reagents, which can adve...
Article
The apparent mass resolution of oligonucleotides in time-of-flight (TOF) mass spectrometers has been examined. In a reflectron TOF instrument, where the isotopic profile can be completely resolved, the apparent resolution matches the instrument's resolving power. In a linear TOF instrument, unresolved isotopic profiles limit the apparent resolution...
Article
The Bacillus stearothermophilus ribosomal protein S15 (BS15) binds both a three-helix junction in the central domain of 16 S ribosomal RNA and its cognate mRNA. Native gel mobility-shift assays show that BS15 interacts specifically and with high affinity to the 5'-untranslated region (5'-UTR) of this cognate mRNA with an apparent dissociation const...
Article
Ten guaianolides, including three previously unreported natural products, were isolated from the aerial parts of Cichorium intybus (Asteraceae), more commonly known as chicory. Two of the new compounds (8 and 9) were analogues of lactupicrin and 11β,13-dihydrolactupicrin, respectively, with the C-15 oxidized to the aldehyde state. The third new na...
Article
This chapter discusses the enzymatic synthesis of specifically labeled ribonucleotide triphosphates (NTPs) for the in vitro transcription of RNA strategy. Isotopically labeled RNAs are prepared in transcription reactions using labeled NTPs and T7 RNA polymerase. Uniformly labeled NTPs are readily produced by the phosphorylation of nucleotides isola...
Thesis
The Turkish traditional medicine Hindiba, prepared from the aerial parts of Cichorium intybus (Asteraceae) has been used for centuries as an anticancer drug. Using the 3H-thymidine incorporation bioassay to monitor the inhibition of cell proliferation in several cancer lines to direct the isolation, 11β,13-dihydrolactucin (1) was isolated as the ac...
Article
Bioassay-guided fractionation of the chloroform/methanol extract of a dart poison from Indonesian Borneo (Kalimantan), derived from Antiaris toxicaria latex, has led to the isolation of two new cardenolides, toxicarioside B [2] and toxicarioside C [3]. Structures for 2 and 3 were deduced by analysis of spectroscopic data; these materials are isomer...
Article
Bioassay-guided fractionation of the chloroform/methanol extract of a dart poison from Indonesian Borneo (Kalimantan), derived from Antiaris toxicaria latex, has led to the isolation of a new cardenolide, toxicarioside A [1]. The structure of 1 was deduced by analysis of spectroscopic data and has led to the first assignment of the 1H- and 13C-NMR...
Article
The ethanolic extract of the seeds of Uvaria tonkinensis (Annonaceae), collected on Hainan Island, have led to the isolation of a new polyoxygenated cyclohexane derivative tonkinenin A [1]. The structure of 1 was deduced from spectroscopic characteristics and the absolute stereochemistry assigned by the O-methylmandelate ester method.
Article
The reactions of indoline (I) and tetrahydroquinoline (THQ) with Os3(CO)10(CH3CN)2 (1) have been studied. Reaction of 1 with I at ambient temperatures gives Os3(CO)10(μ-H)(μ-η2-C8H7NH) (2), which decarbonylates thermally to give a mixture of the tautomeric complexes Os3(CO)9(μ-H)2(μ3-η2-C8H7N) (3 and 4) whose structures differ by having a μ-alkylid...
Article
The guaianolide sesquiterpene pyrethroidinin (1) and the corresponding ketone parishin A (2) wee isolated from Tanacetum densum subsp. amani (Asteraceae). The absolute stereochemistry of 1 was established as (1R, 3R, 6S, 7S, 10R) on the basis of the differential shielfing in the 1H NMR spectra of the (−)- and (+)-O-methylmandelate esters. The struc...
Article
Members of the Tanacetum genus are important medicinal plants found throughout the world which have been used in traditional medicines throughout the world.(1) In Turkey, 44 different species of Tanacetum are known, at least 15 of which are endemic.(2) One such endemic species, T. densum, is further classified into four subspecies: subsp. sivasicum...
Article
The reaction of the mu3-imidoyl clusters (mu-H)(mu3-eta2-CH3C=NCH2CH3)Ru3(CO)9 (1), (mu-H)(mu3-eta2-C=NCH2CH2CH2)Os3(CO)9(2), and (mu-H)(mu-3-eta2-CH3CH2C=NCH2CH2CH3)Os3(CO)9 (3) with CH2N2N2 at 25-degrees-C yield the structurally analogous clusters (mu-H)2(mu3-eta2-CH(CH3)C=NCH2CH3)Ru3(CO)9 (4), (mu-H)2(mu3-eta2-CHC=NCH2CH2CH2)Os3(CO)9 (5), and (m...

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