Professional Education

  • B.A., St. Mary's College of MD, Biology, Chemistry (2006)
  • Doctor of Philosophy, University of Wisconsin Madison (2012)

Stanford Advisors


All Publications

  • Peptides that target protein-protein interactions as an anti-parasite strategy CHIMICA OGGI-CHEMISTRY TODAY Qvit, N., Crapster, J. A. 2014; 32 (6): 31-36
  • Arhgap36-dependent activation of Gli transcription factors. Proceedings of the National Academy of Sciences of the United States of America Rack, P. G., Ni, J., Payumo, A. Y., Nguyen, V., Crapster, J. A., Hovestadt, V., Kool, M., Jones, D. T., Mich, J. K., Firestone, A. J., Pfister, S. M., Cho, Y., Chen, J. K. 2014; 111 (30): 11061-11066


    Hedgehog (Hh) pathway activation and Gli-dependent transcription play critical roles in embryonic patterning, tissue homeostasis, and tumorigenesis. By conducting a genome-scale cDNA overexpression screen, we have identified the Rho GAP family member Arhgap36 as a positive regulator of the Hh pathway in vitro and in vivo. Arhgap36 acts in a Smoothened (Smo)-independent manner to inhibit Gli repressor formation and to promote the activation of full-length Gli proteins. Arhgap36 concurrently induces the accumulation of Gli proteins in the primary cilium, and its ability to induce Gli-dependent transcription requires kinesin family member 3a and intraflagellar transport protein 88, proteins that are essential for ciliogenesis. Arhgap36 also functionally and biochemically interacts with Suppressor of Fused. Transcriptional profiling further reveals that Arhgap36 is overexpressed in murine medulloblastomas that acquire resistance to chemical Smo inhibitors and that ARHGAP36 isoforms capable of Gli activation are up-regulated in a subset of human medulloblastomas. Our findings reveal a new mechanism of Gli transcription factor activation and implicate ARHGAP36 dysregulation in the onset and/or progression of GLI-dependent cancers.

    View details for DOI 10.1073/pnas.1322362111

    View details for PubMedID 25024229

    View details for PubMedCentralID PMC4121843

  • A peptoid ribbon secondary structure. Angewandte Chemie (International ed. in English) Crapster, J. A., Guzei, I. A., Blackwell, H. E. 2013; 52 (19): 5079-5084


    Joining the fold: A series of peptoids, or oligomers of N-substituted glycines, adopt a novel secondary structure, designated the "peptoid ribbon". This fold was stable at short chain lengths and in a variety of solvents (both organic and aqueous), and arose from a primary sequence of peptoid monomers designed to enforce an alternating pattern of cis and trans main-chain amides.

    View details for DOI 10.1002/anie.201208630

    View details for PubMedID 23576308

  • Extraordinarily Robust Polyproline Type I Peptoid Helices Generated via the Incorporation of alpha-Chiral Aromatic N-1-Naphthylethyl Side Chains JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Stringer, J. R., Crapster, J. A., Guzei, I. A., Blackwell, H. E. 2011; 133 (39): 15559-15567


    Peptoids, or oligomers of N-substituted glycines, are a class of foldamers that have shown extraordinary functional potential since their inception nearly two decades ago. However, the generation of well-defined peptoid secondary structures remains a difficult task. This challenge is due, in part, to the lack of a thorough understanding of peptoid sequence-structure relationships and, consequently, an incomplete understanding of the peptoid folding process. We seek to delineate sequence-structure relationships through the systematic study of noncovalent interactions in peptoids and the design of novel amide side chains capable of such interactions. Herein, we report the synthesis and detailed structural analysis of a series of (S)-N-(1-naphthylethyl)glycine (Ns1npe) peptoid homo-oligomers by X-ray crystallography, NMR spectroscopy, and circular dichroism (CD) spectroscopy. Four of these peptoids were found to adopt well-defined structures in the solid state, with dihedral angles similar to those observed in polyproline type I (PPI) peptide helices and in peptoids with α-chiral side chains. The X-ray crystal structure of a representative Ns1npe tetramer revealed an all cis-amide helix, with approximately three residues per turn, and a helical pitch of approximately 6.0 Å. 2D-NMR analysis of the length-dependent Ns1npe series showed that these peptoids have very high overall backbone amide K(cis/trans) values in acetonitrile, indicative of conformationally homogeneous structures in solution. Additionally, CD spectroscopy studies of the Ns1npe homo-oligomers in acetonitrile and methanol revealed a striking length-dependent increase in ellipticity per amide. These Ns1npe helices represent the most robust peptoid helices to be reported, and the incorporation of (S)-N-(1-naphthylethyl)glycines provides a new approach for the generation of stable helical structure in this important class of foldamers.

    View details for DOI 10.1021/ja204755p

    View details for Web of Science ID 000295911500059

    View details for PubMedID 21861531

  • Design and Conformational Analysis of Peptoids Containing N-Hydroxy Amides Reveals a Unique Sheet-Like Secondary Structure BIOPOLYMERS Crapster, J. A., Stringer, J. R., Guzei, I. A., Blackwell, H. E. 2011; 96 (5): 604-616


    N-hydroxy amides can be found in many naturally occurring and synthetic compounds and are known to act as both strong proton donors and chelators of metal cations. We have initiated studies of peptoids, or N-substituted glycines which contain N-hydroxy amide side chains to investigate the potential effects of these functional groups on peptoid backbone amide rotamer equilibria and local conformations. We reasoned that the propensity of these functional groups to participate in hydrogen bonding could be exploited to enforce intramolecular or intermolecular interactions that yield new peptoid structures. Here, we report the design, synthesis, and detailed conformational analysis of a series of model N-hydroxy peptoids. These peptoids were readily synthesized, and their structures were analyzed in solution by 1D and 2D NMR and in the solid-state by X-ray crystallography. The N-hydroxy amides were found to strongly favor trans conformations with respect to the peptoid backbone in chloroform. More notably, unique sheet-like structures held together via intermolecular hydrogen bonds were observed in the X-ray crystal structures of an N-hydroxy amide peptoid dimer, which to our knowledge represent the first structure of this type reported for peptoids. These results suggest that the N-hydroxy amide can be utilized to control both local backbone geometries and longer-range intermolecular interactions in peptoids, and represents a new functional group in the peptoid design toolbox.

    View details for DOI 10.1002/bip.21599

    View details for Web of Science ID 000295385400009

    View details for PubMedID 22180908

  • Construction of Peptoids with All Trans-Amide Backbones and Peptoid Reverse Turns via the Tactical Incorporation of N-Aryl Side Chains Capable of Hydrogen Bonding JOURNAL OF ORGANIC CHEMISTRY Stringer, J. R., Crapster, J. A., Guzei, I. A., Blackwell, H. E. 2010; 75 (18): 6068-6078


    The ability to design foldamers that mimic the defined structural motifs of natural biopolymers is critical for the continued development of functional biomimetic molecules. Peptoids, or oligomers of N-substituted glycine, represent a versatile class of foldamers capable of folding into defined secondary and tertiary structures. However, the rational design of discretely folded polypeptoids remains a challenging task, due in part to an incomplete understanding of the covalent and noncovalent interactions that direct local peptoid folding. We have found that simple, peptoid monomer model systems allow for the effective isolation of individual interactions within the peptoid backbone and side chains and can facilitate the study of the role of these interactions in restricting local peptoid conformation. Herein, we present an analysis of a set of peptoid monomers and an oligomer containing N-aryl side chains capable of hydrogen bonding with the peptoid backbone. These model peptoids were found to exhibit well-defined local conformational preferences, allowing for control of the ω, ϕ, and ψ dihedral angles adopted by the systems. Fundamental studies of the peptoid monomers enabled the design and synthesis of an acyclic peptoid reverse-turn structure, in which N-aryl side chains outfitted with ortho-hydrogen bond donors were hypothesized to play a critical role in the stabilization of the turn. This trimeric peptoid was characterized by X-ray crystallography and 2D NMR spectroscopy and was shown to adopt a unique acyclic peptoid reverse-turn conformation. Further analysis of this turn revealed an n→π*(C═O) interaction within the peptoid backbone, which represents the first reported example of this type of stereoelectronic interaction occurring exclusively within a polypeptoid backbone. The installation of N-aryl side chains capable of hydrogen bonding into peptoids is straightforward and entirely compatible with current solid-phase peptoid synthesis methodologies. As such, we anticipate that the strategic incorporation of these N-aryl side chains should facilitate the construction of peptoids capable of adopting discrete structural motifs, both turnlike and beyond, and will facilitate the continued development of well-folded peptoids.

    View details for DOI 10.1021/jo101075a

    View details for Web of Science ID 000281585600002

    View details for PubMedID 20722367