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1.  Analysis of UDP-D-Apiose/UDP-D-Xylose Synthase-Catalyzed Conversion of UDP-D-Apiose Phosphonate to UDP-D-Xylose Phosphonate: Implications for a Retroaldol-Aldol Mechanism 
Journal of the American Chemical Society  2012;134(34):13946-13949.
UDP-D-apiose/UDP-D-xylose synthase (AXS) catalyzes the conversion of UDP-D-glucuronic acid to UDP-D-apiose and UDP-D-xylose. An acetyl-protected phosphonate analogue of UDP-D-apiose was synthesized and used in an in situ HPLC assay to demonstrate, for the first time, the ability of AXS to interconvert the two reaction products. Density functional theory calculations provided insight into the energetics of this process and the apparent inability of AXS to catalyze the conversion of UDP-D-xylose to UDP-D-apiose. The data suggest that this observation is unlikely to be due to an unfavorable equilibrium, but rather substrate inhibition by the most stable chair conformation of UDP-D-xylose. The detection of xylose cyclic phosphonate as the turnover product uncovers significant new detail about the AXS-catalyzed reaction and supports the proposed retroaldol-aldol mechanism of catalysis.
PMCID: PMC3454503  PMID: 22830643
UDP-D-apiose/UDP-D-xylose synthase; phosphonate substrate analogues; catalytic mechanism
2.  Inter-enzyme substrate diffusion for an enzyme cascade organized on spatially addressable DNA nanostructures 
Spatially addressable DNA nanostructures facilitate the self-assembly of heterogeneous elements with precisely controlled patterns. Here we organized discrete GOx/HRP enzyme pairs on specific DNA origami tiles with controlled inter-enzyme spacing and position. The distance between enzymes was systematically varied from 10 nm to 65 nm and the corresponding activities were evaluated. The study revealed two different distance dependent kinetic processes associated with the assembled enzyme pairs. Strongly enhanced activity was observed for those assemblies in which the enzymes were closely spaced, while the activity dropped dramatically for enzymes as little as 20 nm apart. Increasing the spacing further resulted in a much weaker distance dependence. Combined with diffusion modeling, the results suggest that Brownian diffusion of intermediates in solution governed the variations in activity for more distant enzyme pairs, while dimensionally-limited diffusion of intermediates across connected protein surfaces contributed to the enhancement in activity for closely spaced GOx/HRP assemblies. To further test the role of limited dimensional diffusion along protein surfaces, a noncatalytic protein bridge was inserted between GOx and HRP to connect their hydration shells. This resulted in substantially enhanced activity of the enzyme pair.
PMCID: PMC3319985  PMID: 22414276
3.  Engineering Polymeric Aptamers for Selective Cytotoxicity 
Journal of the American Chemical Society  2011;133(34):13380-13386.
Chemotherapy strategies thus far reported can result in both side effects and drug resistance. To address both of these issues at the cellular level, we report a molecular engineering strategy which employs polymeric aptamers to induce selective cytotoxicity inside target cells. The polymeric aptamers, composed of both multiple cell-based aptamers and a high ratio of dye-labeled short DNA, exploit the target recognition capability of the aptamer, enhanced cell internalization via multivalent effects, and cellular disruption by the polymeric conjugate. Importantly, the polymer backbone built into the conjugate is cytotoxic only inside cells. As a result, selective cytotoxicity is achieved equally in both normal cancer cells and drug-resistant cells. Control assays have confirmed the nontoxicity of the aptamer itself, but they have also shown that the physical properties of the polymer backbone contribute to target cell cytotoxicity. Therefore, our approach may shed new light on drug design and drug delivery.
PMCID: PMC3190636  PMID: 21702469
aptamers; polymerization; cytotoxicity
4.  Proteome Interrogation Using Nanoprobes to Identify Targets of a Cancer-killing Molecule 
We report a generic approach for identification of target proteins of therapeutic molecules using nanoprobes. Nanoprobes verify the integrity of nanoparticle-bound ligands in live cells and pull down target proteins from the cellular proteome, providing very important information on drug targets and mechanisms of action. As an example, target proteins for α-tubulin and HSP 90 were identified and validated.
PMCID: PMC3138543  PMID: 21495622
5.  Dynamic Presentation of Immobilized Ligands Regulated through Biomolecular Recognition 
Journal of the American Chemical Society  2010;132(39):13630-13632.
To mimic the dynamic regulation of signaling ligands immobilized on extracellular matrices or on the surfaces of neighboring cells for guidance of cell behavior and fate selection, we have harnessed biomolecular recognition in combination with polymer engineering to create dynamic surfaces on which the accessibility of immobilized ligands to cell surface receptors can be reversibly interconverted under physiological conditions. The cell-adhesive RGD peptide is chosen as a model ligand. RGD is fused to the C-terminus of a leucine zipper domain A and this fusion polypeptide is immobilized on surfaces through a residue at the N-terminus. The immobilized RGD can be converted from a cell-accessible to a cell-inaccessible state by addition of a conjugate of poly(ethylene) glycol (PEG) and another leucine zipper domain B (B-PEG). Heterodimerization between A and B allows co-immobilization of the PEG, which shields RGD from access by cells. The shielded RGD can be converted back to a cell-accessible state by addition of non-immobilized polypeptide A, which competes with the immobilized A for binding to B-PEG and removes B-PEG from the surface. This molecular design offers several advantages: the interconversion is reversible; the ligand remains immobilized during dynamic regulation so that cells are not exposed to the soluble form of the ligand that potentially has detrimental effects; the precision of the on/off states is assured by the molecular-level uniformity of the ligand and PEG co-immobilized through leucine zipper heterodimerization. The method can be readily adapted for dynamic regulation of other immobilized bioactive ligands of interest.
PMCID: PMC2992805  PMID: 20839864
7.  Molecular Behavior of DNA Origami in Higher-Order Self-Assembly 
Journal of the American Chemical Society  2010;132(38):13545-13552.
DNA-based self-assembly is a unique method for achieving higher-order molecular architectures made possible by the fact that DNA is a programmable information-coding polymer. In the past decade, two main types of DNA nanostructures have been developed: branch-shaped DNA tiles with small dimensions (commonly up to ~20 nm) and DNA origami tiles with larger dimensions (up to ~100 nm). Here we aimed to determine the important factors involved in the assembly of DNA origami superstructures. We constructed a new series of rectangular-shaped DNA origami tiles in which parallel DNA helices are arranged in a zigzag pattern when viewed along the DNA helical axis, a design conceived in order to relax an intrinsic global twist found in the original planar, rectangular origami tiles. Self-associating zigzag tiles were found to form linear arrays in both diagonal directions, while planar tiles showed significant growth in only one direction. Although the series of zigzag tiles were designed to promote two-dimensional array formation, one-dimensional linear arrays and tubular structures were observed instead. We discovered that the dimensional aspect ratio of the origami unit tiles and intertile connection design play important roles in determining the final products, as revealed by atomic force microscopy imaging. This study provides insight into the formation of higher-order structures from self-assembling DNA origami tiles, revealing their unique behavior in comparison with conventional DNA tiles having smaller dimensions.
PMCID: PMC3071357  PMID: 20825190
9.  Multilayer DNA Origami Packed on a Square Lattice 
Molecular self-assembly using DNA as a structural building block has proven to be an efficient route to the construction of nanoscale objects and arrays of increasing complexity. Using the remarkable “scaffolded DNA origami” strategy, Rothemund demonstrated that a long single-stranded DNA from a viral genome (M13) can be folded into a variety of custom two-dimensional (2D) shapes using hundreds of short synthetic DNA molecules as staple strands. More recently, we generalized a strategy to build custom-shaped, three-dimensional (3D) objects formed as pleated layers of helices constrained to a honeycomb lattice, with precisely controlled dimensions ranging from 10 to 100 nm. Here we describe a more compact design for 3D origami, with layers of helices packed on a square lattice, that can be folded successfully into structures of designed dimensions in a one-step annealing process, despite the increased density of DNA helices. A square lattice provides a more natural framework for designing rectangular structures, the option for a more densely packed architecture, and the ability to create surfaces that are more flat than is possible with the honeycomb lattice. Thus enabling the design and construction of custom 3D shapes from helices packed on a square lattice provides a general foundational advance for increasing the versatility and scope of DNA nanotechnology.
PMCID: PMC2821935  PMID: 19807088
12.  Tension Sensing Nanoparticles for Mechano-imaging at the Living Non-living Interface 
Studying chemo-mechanical coupling at interfaces is important for fields ranging from lubrication and tribology to microfluidics and cell biology. Several polymeric macro- and microscopic systems and cantilevers have been developed to image forces at interfaces, but few materials are amenable for molecular tension sensing. To address this issue, we have developed a gold nanoparticle sensor for molecular tension-based fluorescence microscopy (MTFM). As a proof of concept, we imaged the tension exerted by integrin receptors at the interface between living cells and a substrate with high spatial (<1 μm) resolution, at 100 ms acquisition times, and with molecular specificity. We report integrin tension values ranging from 1 to 15 pN and a mean of ~1 pN within focal adhesions. Through the use of a conventional fluorescence microscope, this method demonstrates a force sensitivity that is three orders of magnitude greater than is achievable by traction force microscopy or PDMS micro-post arrays,1 which are the standard in cellular biomechanics.
PMCID: PMC3630457  PMID: 23495954
13.  Nylon-3 Polymers with Selective Antifungal Activity 
Host-defense peptides inhibit bacterial growth but show little toxicity toward mammalian cells. A variety of synthetic polymers have been reported to mimic this antibacterial selectivity; however, achieving comparable selectivity for fungi is more difficult because these pathogens are eukaryotes. Here, we report nylon-3 polymers based on a novel subunit that display potent antifungal activity (MIC = 3.1 μg/mL for C. albicans) and favorable selectivity (IC10 > 400 μg/mL for 3T3 fibroblast toxicity; HC10 > 400 μg/mL for hemolysis).
PMCID: PMC3684071  PMID: 23547967
14.  Guest Packing Motifs within a Supra-molecular Nano-Capsule and a Covalent Analogue 
Two hosts that utilize the hydrophobic effect to assemble and/or encapsulate guest molecules were studied. The hosts, octa-acid (OA) and hexalene diamine-linked octa-acid (HOA) were shown to complex a broad range of n-alkanes up to n-hexacosane (C26H54). A combination of 1H NMR, NMR diffusion, COSY, and NOESY experiments revealed four different guest packing motifs, depending on the size of the guest and the nature of the host. As a function of guest size, smooth transitions from one motif to the next were observed and allowed qualification of their relative stabilities. Furthermore, although the two hosts engender ostensibly identical encapsulation environments, their different assembly properties lead to quite distinct packing-motif profiles, i.e., how the motifs change as a function of guest size.
PMCID: PMC3613047  PMID: 23448338
15.  Comparison of High-Spin and Low-Spin Non-heme FeIII–OOH Complexes in O–O Bond Homolysis and H-atom Abstraction Reactivities 
The geometric and electronic structures and reactivity of an S = 5/2 (HS) mononuclear non-heme (TMC)FeIII–OOH complex are studied by spectroscopies, calculations, and kinetics and compared with the results of previous studies of S = 1/2 (LS) FeIII–OOH complexes to understand parallels and differences in mechanisms of O–O bond homolysis and electrophilic H-atom abstraction reactions. The homolysis reaction of the HS [(TMC)FeIII–OOH]2+ complex is found to involve axial ligand coordination and a crossing to the LS surface for O–O bond homolysis. Both HS and LS FeIII–OOH complexes are found to perform direct H-atom abstraction reactions but with very different reaction coordinates. For the LS FeIII–OOH, the transition state is late in O–O and early in C–H coordinates. However, for the HS FeIII–OOH, the transition state is early in O–O and further along in the C–H coordinate. In addition, there is a significant amount of electron transfer from the substrate to the HS FeIII–OOH at transition state, but that does not occur in the LS transition state. Thus, in contrast to the behavior of LS FeIII–OOH, the H-atom abstraction reactivity of HS FeIII–OOH is found to be highly dependent on both the ionization potential and C–H bond strength of the substrate. LS FeIII–OOH is found to be more effective in H-atom abstraction for strong C–H bonds, while the higher reduction potential of HS FeIII–OOH allows it to be active in electrophilic reactions without the requirement of O–O bond cleavage. This is relevant to the Rieske dioxygenases, which are proposed to use a HS FeIII–OOH to catalyze cis-dihydroxylation of a wide range of aromatic compounds.
PMCID: PMC3614352  PMID: 23368958
16.  A Genetically Encoded AND Gate for Cell-Targeted Metabolic Labeling of Proteins 
We describe a genetic AND gate for cell-targeted metabolic labeling and proteomic analysis in complex cellular systems. The centerpiece of the AND gate is a bisected methionyl-tRNA synthetase (MetRS) that charges the Met surrogate azidonorleucine (Anl) to tRNAMet. Cellular protein labeling occurs only upon activation of two different promoters that drive expression of the N- and C-terminal fragments of the bisected MetRS. Anl-labeled proteins can be tagged with fluorescent dyes or affinity reagents via either copper-catalyzed or strain-promoted azide-alkyne cycloaddition. Protein labeling is apparent within five minutes after addition of Anl to bacterial cells in which the AND gate has been activated. This method allows spatial and temporal control of proteomic labeling and identification of proteins made in specific cellular subpopulations. The approach is demonstrated by selective labeling of proteins in bacterial cells immobilized in the center of a laminar-flow microfluidic channel, where they are exposed to overlapping, opposed gradients of inducers of the N- and C-terminal MetRS fragments. The observed labeling profile is predicted accurately from the strengths of the individual input signals.
PMCID: PMC3620012  PMID: 23406315
17.  Design and synthesis of curcumin analogues for in vivo fluorescence imaging and inhibiting copper-induced cross-linking of amyloid beta species in Alzheimer's disease 
Journal of the American Chemical Society  2013;135(44):16397-16409.
In this article, we first designed and synthesized curcumin-based near infrared (NIR) fluorescence imaging probes for detecting both soluble and insoluble amyloid beta (Aβ) species, and then an inhibitor that could attenuate crosslinking of Aβ induced by copper. According to our previous results and the possible structural stereo-hindrance compatibility of the Aβ peptide and the hydrophobic/hydrophilic property of the Aβ13–20 (HHQKLVFF) fragment, NIR imaging probe CRANAD-58 was designed and synthesized. As expected CRANAD-58 showed significant fluorescence property changes upon mixing with both soluble and insoluble Aβ species in vitro. In vivo NIR imaging revealed that CRANAD-58 was capable of differentiating transgenic and wild type mice as young as 4-months old, the age that lacks apparently visible Aβ plaques and Aβ is likely in its soluble forms. In this report, according to our limited studies on the interaction mechanism between CRANAD-58 and Aβ, we also designed CRANAD-17 to attenuate the crosslinking of Aβ42 induced by copper. It is well known that the coordination of copper with imidazoles on Histidine-13 and 14 (H13, H14) of Aβ peptides could initialize covalent crosslinking of Aβ. In CRANAD-17, a curcumin scaffold was used as an anchoring moiety to usher the designed compound to the vicinity of H13 and H14 of Aβ, and imidazole rings were incorporated to compete with H13/H14 for copper binding. The results of SDS-PAGE gel and Western blot indicated that CRANAD-17 was capable of inhibiting Aβ42 cross-linking induced by copper. This raises a potential for CRANAD-17 to be considered for AD therapy.
PMCID: PMC3927838  PMID: 24116384
18.  Asymmetric Ligand Binding Facilitates Conformational Transitions in Pentameric Ligand-Gated Ion Channels 
The anesthetic propofol inhibits the currents of the homo-pentameric ligand-gated ion channel GLIC, yet the crystal structure of GLIC with five propofol molecules bound symmetrically shows an open-channel conformation. To address this dilemma and determine if symmetry of propofol binding sites affects the channel conformational transition, we performed a total of 1.5 As of molecular dynamics simulations for different GLIC systems with propofol occupancies of 0, 1, 2, 3, and 5. GLIC without propofol binding or with five propofol molecules bound symmetrically showed similar channel conformation and hydration status over multiple replicates of 100-ns simulations. In contrast, asymmetric binding to one, two or three equivalent sites in different subunits accelerated the channel dehydration, which was accompanied by increased conformational heterogeneity of the pore and shifted the lateral and radial tilting angles of the pore-lining TM2 towards a closed-channel conformation. The results differentiate two groups of systems based on the propofol binding symmetry. The difference between symmetric and asymmetric groups is correlated with the variance in the propofol-binding cavity adjacent to the hydrophobic gate and the force imposed by the bound propofol. Asymmetrically bound propofol produced greater variance in the cavity size that could further elevate the conformation heterogeneity. The force trajectory generated by propofol in each subunit over the course of a simulation exhibits an ellipsoidal shape, which has the larger component tangential to the pore. Asymmetric propofol binding creates an unbalanced force that expedites the channel conformation transitions. The findings from this study not only suggest that asymmetric binding underlies the propofol functional inhibition of GLIC, but also advocate for the role of symmetry breaking in facilitating channel conformational transitions.
PMCID: PMC3582375  PMID: 23339564
anesthetics; propofol; GLIC; pLGICs; ion channels; molecular dynamics
19.  Transforming thymidine into a magnetic resonance imaging probe for monitoring gene expression 
Synthetic chemistry has revolutionized the understanding of many biological systems. Small compounds that act as agonists and antagonists of proteins, and occasionally as imaging probes, have contributed tremendously to the elucidation of many biological pathways. Nevertheless, the function of thousands of proteins is still elusive, and designing new imaging probes remains a challenge. Through screening and characterization we identified thymidine analog as probe for imaging the expression of the Herpes Simplex Virus type-1 thymidine kinase (HSV1-TK). To detect the probe, we used chemical exchange saturation transfer magnetic resonance imaging (CEST-MRI), in which a dynamic exchange process between an exchangeable proton and the surrounding water protons is used to amplify the desired contrast. Initially, five pyrimidine-based molecules were recognized as putative imaging agents, since their exchangeable imino protons resonate at 5–6ppm from the water proton frequency and their detection is therefore less affected by endogenous CEST contrast or confounded by direct water saturation. Increasing the pKa value of the imino proton by reduction of its 5,6-double bond results in a significant reduction of the exchange rate (kex) between this proton and the water protons. This reduced kex of the dihydropyrimidine nucleosides fulfills the “slow to intermediate regime” condition for generating high CEST-MRI contrast. Consequently, we identified 5-methyl-5,6-dihydrothymidine as the optimal probe and demonstrated its feasibility for in vivo imaging of the HSV1-TK. In light of these findings, this new approach can be generalized for designing specific probes for the in vivo imaging of a variety of proteins and enzymes.
PMCID: PMC3560322  PMID: 23289583
20.  Profiling Genome-wide Chromatin Methylation with Engineered Posttranslation Apparatus within Living Cells 
Protein methyltransferases (PMTs) have emerged as important epigenetic regulators in myriad biological processes both in normal physiology and disease conditions. However, elucidating PMT-regulated epigenetic processes has been hampered by ambiguous knowledge about in vivo activities of individual PMTs particularly because of their overlapping but non-redundant functions. To address limitations of conventional approaches in mapping chromatin modification of specific PMTs, we have engineered the chromatin-modifying apparatus and formulated a novel technology, termed Clickable Chromatin Enrichment with parallel DNA sequencing (CliEn-seq), to probe genome-wide chromatin modification within living cells. The three-step approach of CliEn-seq involves in vivo synthesis of S-adenosyl-L-methionine (SAM) analogues from cell-permeable methionine analogues by engineered SAM synthetase (methionine adenosyltransferase or MAT), in situ chromatin modification by engineered PMTs, subsequent enrichment and sequencing of the uniquely modified chromatins. Given critical roles of the chromatin-modifying enzymes in epigenetics and structural similarity among many PMTs, we envision that the CliEn-seq technology is generally applicable in deciphering chromatin methylation events of individual PMTs in diverse biological settings.
PMCID: PMC3582175  PMID: 23244065
21.  Design of DNA Minor Groove Binding Diamidines that Recognize GC base pair Sequences: A Dimeric-Hinge Interaction Motif 
Journal of the American Chemical Society  2007;129(44):10.1021/ja074560a.
The classical model of DNA minor groove binding compounds is that they should have a crescent shape that closely fits the helical twist of the groove. Several compounds with relatively linear shape and large dihedral twist, however, have been found recently to bind strongly to the minor groove. These observations raise the question of how far the curvature requirement could be relaxed. As an initial step in experimental analysis of this question, a linear triphenyl diamidine, DB1111 and a series of nitrogen tricyclic analogues were prepared. The goal with the heterocycles is to design GC binding selectivity into heterocyclic compounds that can get into cells and exert biological effects. The compounds have a zero radius of curvature from amidine carbon to amidine carbon but a significant dihedral twist across the tricyclic and amidine-ring junctions. They would not be expected to bind well to the DNA minor groove by shape-matching criteria. Detailed DNaseI footprinting studies of the sequence specificity of this set of diamidines indicated that a pyrimidine heterocyclic derivative, DB1242, has remarkable binding specificity for a GC rich sequence, -GCTCG-. It binds to the GC sequence more strongly than to the usual AT recognition sequences for curved minor groove agents. Other similar derivatives did not exhibit the GC specificity. Biosensor-surface plasmon resonance and isothermal titration calorimetry experiments indicate that DB1242 binds to the GC sequence as a highly cooperative stacked dimer. Circular dichroism results indicate that the compound binds in the minor groove. Molecular modeling studies support a minor groove complex and provide an inter-compound and compound-DNA hydrogen bonding rational for the unusual GC binding specificity and the requirement for a pyrimidine heterocycle. This compound represents a new direction in development of DNA sequence specific agents and it is the first non-polyamide, synthetic compound to specifically recognize a DNA sequence with a majority of GC base pairs.
PMCID: PMC3865524  PMID: 17935330
22.  Dynamics of Bleomycin Interaction with a Strongly Bound Hairpin DNA Substrate, and Implications for Cleavage of the Bound DNA 
Journal of the American Chemical Society  2012;134(43):10.1021/ja306233e.
Recent studies involving DNAs bound strongly by bleomycins have documented that such DNAs are degraded by the antitumor antibiotic with characteristics different from those observed when studying the cleavage of randomly chosen DNAs in the presence of excess Fe•BLM. In the present study, surface plasmon resonance has been used to characterize the dynamics of BLM B2 binding to a strongly bound hairpin DNA, to define the effects of Fe3+, salt and temperature on BLM–DNA interaction. One strong primary DNA binding site, and at least one much weaker site was documented. In contrast, more than one strong cleavage site was found, an observation also made for two other hairpin DNAs. Evidence is presented for BLM equilibration between the stronger and weaker binding sites in a way that renders BLM unavailable to other, less strongly bound DNAs. Thus enhanced binding to a given site does not necessarily result in increased DNA degradation at that site, i.e. for strongly bound DNAs, the facility of DNA cleavage must involve parameters in addition to the intrinsic rate of C-4′ H atom abstraction from DNA sugars.
PMCID: PMC3840713  PMID: 23072568
23.  Bright Core-Shell Semiconductor Quantum Wires 
Journal of the American Chemical Society  2012;134(45):18797-18803.
Colloidal CdTe quantum wires are reported having ensemble photoluminescence efficiencies as high as 25% under low excitation-power densities. High photoluminescence efficiencies are achieved by formation of a monolayer CdS shell on the CdTe quantum wires. Like other semiconductor nanowires, the CdTe quantum wires may contain frequent wurtzite–zinc-blende structural alternations along their lengths. The present results demonstrate that the optical properties, emission-peak shape and photoluminescence efficiencies, are independent of the presence or absence of such structural alternations.
PMCID: PMC3508702  PMID: 23095017
24.  A Highly Selective and Potent PTP-MEG2 Inhibitor with Therapeutic Potential for Type 2 Diabetes 
Journal of the American Chemical Society  2012;134(43):18116-18124.
Protein tyrosine phosphatases (PTPs) constitute a large family of signaling enzymes that control the cellular levels of protein tyrosine phosphorylation. A detailed understanding of PTP functions in normal physiology and in pathogenic conditions has been hampered by the absence of PTP-specific, cell-permeable small molecule agents. We present a stepwise focused library approach that transforms a weak and general nonhydrolyzable pTyr mimetic (F2Pmp, phosphonodifluoromethyl phenylalanine) into a highly potent and selective inhibitor of PTP-MEG2, an antagonist of hepatic insulin signaling. The crystal structures of the PTP-MEG2-inhibitor complexes provide direct evidence that potent and selective PTP inhibitors can be obtained by introducing molecular diversity into the F2Pmp scaffold to engage both the active site and unique nearby peripheral binding pockets. Importantly, the PTP-MEG2 inhibitor possesses highly efficacious cellular activity and is capable of augmenting insulin signaling and improving insulin sensitivity and glucose homeostasis in diet-induced obese mice. The results indicate that F2Pmp can be converted into highly potent and selective PTP inhibitory agents with excellent in vivo efficacy. Given the general nature of the approach, this strategy should be applicable to other members of the PTP superfamily.
PMCID: PMC3505080  PMID: 23075115
25.  Turning a Scorpion Toxin into an Antitumor Miniprotein 
Journal of the American Chemical Society  2008;130(41):10.1021/ja8042036.
PMCID: PMC3810402  PMID: 18798622

Results 1-25 (210)