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Jennifer M. Heemstra

Bio: Jennifer M. Heemstra is an academic researcher from Emory University. The author has contributed to research in topics: Aptamer & RNA. The author has an hindex of 23, co-authored 72 publications receiving 1442 citations. Previous affiliations of Jennifer M. Heemstra include Georgia Institute of Technology & Harvard University.


Papers
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Journal ArticleDOI
TL;DR: The generalization of this experimental approach, the chain-length dependence test, is useful for studying solution conformation, packing in the solid state, specific intrachain interactions, and the contributions of end groups to a particular property.
Abstract: Trends obtained from systematic studies based on chain-length variation have provided valuable insight and understanding into the behavior of m-phenylene ethynylene foldamers. The generalization of this experimental approach, the chain-length dependence test, is useful for studying solution conformation, packing in the solid state, specific intrachain interactions, and the contributions of end groups to a particular property.

164 citations

Journal ArticleDOI
TL;DR: An aptamer-based analogue of the widely used sandwich enzyme-linked immunosorbent assay (ELISA) that demonstrates detection of cocaine at concentrations of 100 nM-100 μM in buffer and 1- 100 μM human blood serum and highlights the utility of covalently trapping split aptamer assembly events.
Abstract: Here we report an aptamer-based analogue of the widely used sandwich enzyme-linked immunosorbent assay (ELISA). This assay utilizes the cocaine split aptamer, which is comprised of two DNA strands that only assemble in the presence of the target small molecule. One split aptamer fragment is immobilized on a microplate, then a test sample is added containing the second split aptamer fragment. If cocaine is present in the test sample, it directs assembly of the split aptamer and promotes a chemical ligation between azide and cyclooctyne functional groups appended to the termini of the split aptamer fragments. Ligation results in covalent attachment of biotin to the microplate and provides a colorimetric output upon conjugation to streptavidin–horseradish peroxidase. Using this assay, we demonstrate detection of cocaine at concentrations of 100 nM–100 μM in buffer and 1–100 μM human blood serum. The detection limit of 1 μM in serum represents an improvement of two orders of magnitude over previously reported...

107 citations

Journal ArticleDOI
TL;DR: Two methods to detect in a broad manner chemically labile cellular small molecule–RNA conjugates are developed and suggest that the chemical diversity of cellular RNA may be greater than previously understood.
Abstract: Compared with the rapidly expanding set of known biological roles for RNA, the known chemical diversity of cellular RNA has remained limited primarily to canonical RNA, 3′-aminoacylated tRNAs, nucleobase-modified RNAs, and 5′-capped mRNAs in eukaryotes. We developed two methods to detect in a broad manner chemically labile cellular small molecule–RNA conjugates. The methods were validated by the detection of known tRNA and rRNA modifications. The first method analyzes small molecules cleaved from RNA by base or nucleophile treatment. Application to Escherichia coli and Streptomyces venezuelae RNA revealed an RNA-linked hydroxyfuranone or succinyl ester group, in addition to a number of other putative small molecule–RNA conjugates not previously reported. The second method analyzes nuclease-generated mononucleotides before and after treatment with base or nucleophile and also revealed a number of new putative small molecule–RNA conjugates, including 3′-dephospho-CoA and its succinyl-, acetyl-, and methylmalonyl-thioester derivatives. Subsequent experiments established that these CoA species are attached to E. coli and S. venezuelae RNA at the 5′ terminus. CoA-linked RNA cannot be generated through aberrant transcriptional initiation by E. coli RNA polymerase in vitro, and CoA-linked RNA in E. coli is only found among smaller (≲200 nucleotide) RNAs that have yet to be identified. These results provide examples of small molecule-RNA conjugates and suggest that the chemical diversity of cellular RNA may be greater than previously understood.

103 citations

PatentDOI
TL;DR: In this paper, a method for detecting small molecules in a sample can include reacting together a first half of a DNA split aptamer having a first reactive group coupled to the small molecule, and a second half of an aptamer with a second reactive group.
Abstract: Methods, assays, and products for the detection of small molecules are provided. In one aspect, for example, a method of detecting a small molecule in a sample can include reacting together a first half of a DNA split aptamer having a first reactive group coupled thereto, a second half of a DNA split aptamer having a second reactive group coupled thereto, where the DNA split aptamer is selective for the small molecule, and a sample containing the small molecule. The first half and the second half bind to the small molecule and the first reactive group and the second reactive group react to form an aptamer ligation product of the first half and the second half. The method can also include assaying for the aptamer ligation product in order to detect the small molecule presence in the sample.

87 citations

Journal ArticleDOI
TL;DR: This research establishes the first example of an XNA aptamer of any kind to be evolved having affinity to a small-molecule target, as well as its high level of selectivity, as it is capable of binding OTA in a large background of competing biomolecules.
Abstract: Despite advances in XNA evolution, the binding capabilities of artificial genetic polymers are currently limited to protein targets. Here, we describe the expansion of in vitro evolution techniques to enable selection of threose nucleic acid (TNA) aptamers to ochratoxin A (OTA). This research establishes the first example of an XNA aptamer of any kind to be evolved having affinity to a small-molecule target. Selection experiments against OTA yielded aptamers having affinities in the mid nanomolar range; with the best binders possessing KD values comparable to or better than those of the best previously reported DNA aptamer to OTA. Importantly, the TNA can be incubated in 50% human blood serum for seven days and retain binding to OTA with only a minor change in affinity, while the DNA aptamer is completely degraded and loses all capacity to bind the target. This not only establishes the remarkable biostability of the TNA aptamer, but also its high level of selectivity, as it is capable of binding OTA in a large background of competing biomolecules. Together, this research demonstrates that refining methods for in vitro evolution of XNA can enable the selection of aptamers to a broad range of increasingly challenging target molecules.

76 citations


Cited by
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01 Jan 2011
TL;DR: The sheer volume and scope of data posed by this flood of data pose a significant challenge to the development of efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data.
Abstract: Rapid improvements in sequencing and array-based platforms are resulting in a flood of diverse genome-wide data, including data from exome and whole-genome sequencing, epigenetic surveys, expression profiling of coding and noncoding RNAs, single nucleotide polymorphism (SNP) and copy number profiling, and functional assays. Analysis of these large, diverse data sets holds the promise of a more comprehensive understanding of the genome and its relation to human disease. Experienced and knowledgeable human review is an essential component of this process, complementing computational approaches. This calls for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data. However, the sheer volume and scope of data pose a significant challenge to the development of such tools.

2,187 citations

Journal ArticleDOI
TL;DR: This review describes a multidimensional treatment of molecular recognition phenomena involving aromatic rings in chemical and biological systems that facilitates the development of new advanced materials and supramolecular systems, and should inspire further utilization of interactions with aromatic rings to control the stereochemical outcome of synthetic transformations.
Abstract: This review describes a multidimensional treatment of molecular recognition phenomena involving aromatic rings in chemical and biological systems. It summarizes new results reported since the appearance of an earlier review in 2003 in host-guest chemistry, biological affinity assays and biostructural analysis, data base mining in the Cambridge Structural Database (CSD) and the Protein Data Bank (PDB), and advanced computational studies. Topics addressed are arene-arene, perfluoroarene-arene, S⋅⋅⋅aromatic, cation-π, and anion-π interactions, as well as hydrogen bonding to π systems. The generated knowledge benefits, in particular, structure-based hit-to-lead development and lead optimization both in the pharmaceutical and in the crop protection industry. It equally facilitates the development of new advanced materials and supramolecular systems, and should inspire further utilization of interactions with aromatic rings to control the stereochemical outcome of synthetic transformations.

1,221 citations

Journal ArticleDOI
TL;DR: New features are included: a census of human and yeast snoRNAs involved in RNA-guided RNA modification, a new section covering the 5′-end capping process, and a catalogue of ‘building blocks’ for chemical synthesis of a large variety of modified nucleosides.
Abstract: MODOMICS is a database of RNA modifications that provides comprehensive information concerning the chemical structures of modified ribonucleosides, their biosynthetic pathways, RNA-modifying enzymes and location of modified residues in RNA sequences. In the current database version, accessible at http://modomics.genesilico.pl, we included new features: a census of human and yeast snoRNAs involved in RNA-guided RNA modification, a new section covering the 5′-end capping process, and a catalogue of ‘building blocks’ for chemical synthesis of a large variety of modified nucleosides. The MODOMICS collections of RNA modifications, RNA-modifying enzymes and modified RNAs have been also updated. A number of newly identified modified ribonucleosides and more than one hundred functionally and structurally characterized proteins from various organisms have been added. In the RNA sequences section, snRNAs and snoRNAs with experimentally mapped modified nucleosides have been added and the current collection of rRNA and tRNA sequences has been substantially enlarged. To facilitate literature searches, each record in MODOMICS has been cross-referenced to other databases and to selected key publications. New options for database searching and querying have been implemented, including a BLAST search of protein sequences and a PARALIGN search of the collected nucleic acid sequences.

911 citations

Journal Article
TL;DR: This paper showed that template-directed calcium carbonate formation starts with the formation of prenucleation clusters and their aggregation leads to the nucleation of amorphous nanoparticles in solution.
Abstract: Biogenic calcium carbonate forms the inorganic component of seashells, otoliths, and many marine skeletons, and its formation is directed by an ordered template of macromolecules. Classical nucleation theory considers crystal formation to occur from a critical nucleus formed by the assembly of ions from solution. Using cryotransmission electron microscopy, we found that template-directed calcium carbonate formation starts with the formation of prenucleation clusters. Their aggregation leads to the nucleation of amorphous nanoparticles in solution. These nanoparticles assemble at the template and, after reaching a critical size, develop dynamic crystalline domains, one of which is selectively stabilized by the template. Our findings have implications for template-directed mineral formation in biological as well as in synthetic systems.

719 citations