Matthew B. Francis

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Name: Francis, Matthew B.

Organization: University of California , USA

Department: Department of Chemistry

Title: (PhD)

Chemicals
References

Hyperpolarized Xenon-Based Molecular Sensors for Label-Free Detection of analytes

Co-reporter:Praveena D. Garimella ; Tyler Meldrum ; Leah S. Witus ; Monica Smith ; Vikram S. Bajaj ; David E. Wemmer ; Matthew B. Francis ;Alexander Pines

Journal of the American Chemical Society 2013 Volume 136(Issue 1) pp:164-168

Publication Date(Web):December 6, 2013

DOI:10.1021/ja406760r

Nuclear magnetic resonance (NMR) can reveal the chemical constituents of a complex mixture without resorting to chemical modification, separation, or other perturbation. Recently, we and others have developed magnetic resonance agents that report on the presence of dilute analytes by proportionately altering the response of a more abundant or easily detected species, a form of amplification. One example of such a sensing medium is xenon gas, which is chemically inert and can be optically hyperpolarized, a process that enhances its NMR signal by up to 5 orders of magnitude. Here, we use a combinatorial synthetic approach to produce xenon magnetic resonance sensors that respond to small molecule analytes. The sensor responds to the ligand by producing a small chemical shift change in the Xe NMR spectrum. We demonstrate this technique for the dye, Rhodamine 6G, for which we have an independent optical assay to verify binding. We thus demonstrate that specific binding of a small molecule can produce a xenon chemical shift change, suggesting a general approach to the production of xenon sensors targeted to small molecule analytes for in vitro assays or molecular imaging in vivo.

Multivalent, High-Relaxivity MRI Contrast Agents Using Rigid Cysteine-Reactive Gadolinium Complexes

Co-reporter:Praveena D. Garimella ; Ankona Datta ; Dante W. Romanini ; Kenneth N. Raymond

Journal of the American Chemical Society 2011 Volume 133(Issue 37) pp:14704-14709

Publication Date(Web):July 29, 2011

DOI:10.1021/ja204516p

MRI contrast agents providing very high relaxivity values can be obtained through the attachment of multiple gadolinium(III) complexes to the interior surfaces of genome-free viral capsids. In previous studies, the contrast enhancement was predicted to depend on the rigidity of the linker attaching the MRI agents to the protein surface. To test this hypothesis, a new set of Gd-hydroxypyridonate based MRI agents was prepared and attached to genetically introduced cysteine residues through flexible and rigid linkers. Greater contrast enhancements were seen for MRI agents that were attached via rigid linkers, validating the design concept and outlining a path for future improvements of nanoscale MRI contrast agents.

Oxidative Modification of Native Protein Residues Using Cerium(IV) Ammonium Nitrate

Co-reporter:Kristen L. Seim ; Allie C. Obermeyer

Journal of the American Chemical Society 2011 Volume 133(Issue 42) pp:16970-16976

Publication Date(Web):October 3, 2011

DOI:10.1021/ja206324q

A new protein modification strategy has been developed that is based on an oxidative coupling reaction that targets electron-rich amino acids. This strategy relies on cerium(IV) ammonium nitrate (CAN) as an oxidation reagent and results in the coupling of tyrosine and tryptophan residues to phenylene diamine and anisidine derivatives. The methodology was first identified and characterized on peptides and small molecules, and was subsequently adapted for protein modification by determining appropriate buffer conditions. Using the optimized procedure, native and introduced solvent-accessible residues on proteins were selectively modified with polyethylene glycol (PEG) and small peptides. This unprecedented bioconjugation strategy targets these under-utilized amino acids with excellent chemoselectivity and affords good-to-high yields using low concentrations of the oxidant and coupling partners, short reaction times, and mild conditions.

Nanoscale Protein Assemblies from a Circular Permutant of the Tobacco Mosaic Virus

Co-reporter:Michel T. Dedeo, Karl E. Duderstadt, James M. Berger and Matthew B. Francis

Nano Letters 2010 Volume 10(Issue 1) pp:181-186

Publication Date(Web):November 19, 2009

DOI:10.1021/nl9032395

The protein coat of the tobacco mosaic virus (TMV) has been explored extensively for the construction of nanoscale architectures. In previous work, we have reported efficient TMV-based light harvesting systems bearing chromophores in a hollow channel of the assembled protein. We have also reported an N-terminal transamination/oximation method that could be used to attach electrodes and catalytic groups to the exterior surface of the rods. To complement these techniques, we report herein a new circular permutant of the TMV capsid protein that repositions the N- and C-termini to the center of the assemblies. This protein can be produced in very high yield through E. coli expression and self-assembles into light harvesting rods that are much like those assembled from the wild-type protein. However, the disks formed from the permutant structure are stable over a significantly wider pH range, greatly improving the practicality of this assembled form for materials applications. The new position of the N-terminus allows functional groups to be installed in the inner pore of the disks, affording geometries reminiscent of natural photosynthetic systems. The permutant also shows the ability to coassemble with regular monomers, allowing the future generation of multicomponent rod structures that are modified on the exterior and interior surfaces, as well as in the internal RNA channel.

Immobilization and One-Dimensional Arrangement of Virus Capsids with Nanoscale Precision Using DNA Origami

Co-reporter:Nicholas Stephanopoulos, Minghui Liu, Gary J. Tong, Zhe Li, Yan Liu, Hao Yan and Matthew B. Francis

Nano Letters 2010 Volume 10(Issue 7) pp:2714-2720

Publication Date(Web):June 24, 2010

DOI:10.1021/nl1018468

DNA origami was used as a scaffold to arrange spherical virus capsids into one-dimensional arrays with precise nanoscale positioning. To do this, we first modified the interior surface of bacteriophage MS2 capsids with fluorescent dyes as a model cargo. An unnatural amino acid on the external surface was then coupled to DNA strands that were complementary to those extending from origami tiles. Two different geometries of DNA tiles (rectangular and triangular) were used. The capsids associated with tiles of both geometries with virtually 100% efficiency under mild annealing conditions, and the location of capsid immobilization on the tile could be controlled by the position of the probe strands. The rectangular tiles and capsids could then be arranged into one-dimensional arrays by adding DNA strands linking the corners of the tiles. The resulting structures consisted of multiple capsids with even spacing (∼100 nm). We also used a second set of tiles that had probe strands at both ends, resulting in a one-dimensional array of alternating capsids and tiles. This hierarchical self-assembly allows us to position the virus particles with unprecedented control and allows the future construction of integrated multicomponent systems from biological scaffolds using the power of rationally engineered DNA nanostructures.

Identification of Highly Reactive Sequences For PLP-Mediated Bioconjugation Using a Combinatorial Peptide Library

Co-reporter:Leah S. Witus ; Troy Moore ; Benjamin W. Thuronyi ; Aaron P. Esser-Kahn ; Rebecca A. Scheck ; Anthony T. Iavarone

Journal of the American Chemical Society 2010 Volume 132(Issue 47) pp:16812-16817

Publication Date(Web):November 10, 2010

DOI:10.1021/ja105429n

Chemical reactions that facilitate the attachment of synthetic groups to proteins are useful tools for the field of chemical biology and enable the incorporation of proteins into new materials. We have previously reported a pyridoxal 5′-phosphate (PLP)-mediated reaction that site-specifically oxidizes the N-terminal amine of a protein to afford a ketone. This unique functional group can then be used to attach a reagent of choice through oxime formation. Since its initial report, we have found that the N-terminal sequence of the protein can significantly influence the overall success of this strategy. To obtain short sequences that lead to optimal conversion levels, an efficient method for the evaluation of all possible N-terminal amino acid combinations was needed. This was achieved by developing a generalizable combinatorial peptide library screening platform suitable for the identification of sequences that display high levels of reactivity toward a desired bioconjugation reaction. In the context of N-terminal transamination, a highly reactive alanine−lysine motif emerged, which was confirmed to promote the modification of peptide substrates with PLP. This sequence was also tested on two protein substrates, leading to substantial increases in reactivity relative to their wild-type termini. This readily encodable tripeptide thus appears to provide a significant improvement in the reliability with which the PLP-mediated bioconjugation reaction can be used. This study also provides an important first example of how synthetic peptide libraries can accelerate the discovery and optimization of protein bioconjugation strategies.

Incorporation of Antifreeze Proteins into Polymer Coatings Using Site-Selective Bioconjugation

Co-reporter:Aaron P. Esser-Kahn ; Vivian Trang

Journal of the American Chemical Society 2010 Volume 132(Issue 38) pp:13264-13269

Publication Date(Web):September 8, 2010

DOI:10.1021/ja103038p

The diverse functional repertoire of proteins promises to yield new materials with unprecedented capabilities, so long as versatile chemical methods are available to introduce synthetic components at specific sites on biomolecule surfaces. As a demonstration of this potential, we have used site-selective strategies to attach antifreeze proteins found in Arctic fish and insects to polymer chains. This multivalent arrangement increases the thermal hysteresis activity of the proteins and leads to materials that can be cast into thin films. The polymer−protein conjugates retain the ability of the proteins to slow ice growth in subzero water and can inhibit ice formation after attachment to glass surfaces. These inexpensive materials may prove useful as coatings for device components that must function at low temperature without ice buildup. The polymer attachment also allows higher thermal hysteresis values to be achieved while using less protein, thus lowering the cost of these additives for biomedical applications.

Impact of Assembly State on the Defect Tolerance of TMV-Based Light Harvesting Arrays

Co-reporter:Rebekah A. Miller ; Nicholas Stephanopoulos ; Jesse M. McFarland ; Andrew S. Rosko ; Phillip L. Geissler

Journal of the American Chemical Society 2010 Volume 132(Issue 17) pp:6068-6074

Publication Date(Web):April 14, 2010

DOI:10.1021/ja909566z

Self-assembling, light harvesting arrays of organic chromophores can be templated using the tobacco mosaic virus coat protein (TMVP). The efficiency of energy transfer within systems containing a high ratio of donors to acceptors shows a strong dependence on the TMVP assembly state. Rod and disk assemblies derived from a single stock of chromophore-labeled protein exhibit drastically different levels of energy transfer, with rods significantly outperforming disks. The origin of the superior transfer efficiency was probed through the controlled introduction of photoinactive conjugates into the assemblies. The efficiency of the rods showed a linear dependence on the proportion of deactivated chromophores, suggesting the availability of redundant energy transfer pathways that can circumvent defect sites. Similar disk-based systems were markedly less efficient at all defect levels. To examine these differences further, the brightness of donor-only systems was measured as a function of defect incorporation. In rod assemblies, the photophysical properties of the donor chromophores showed a significant dependence on the number of defects. These differences can be partly attributed to vertical energy transfer events in rods that occur more rapidly than the horizontal transfers in disks. Using these geometries and the previously measured energy transfer rates, computational models were developed to understand this behavior in more detail and to guide the optimization of future systems. These simulations have revealed that significant differences in excited state dissipation rates likely also contribute to the greater efficiency of the rods and that statistical variations in the assembly process play a more minor role.

Dramatic Thermal Stability of Virus−Polymer Conjugates in Hydrophobic Solvents

Co-reporter:Patrick G. Holder, Daniel T. Finley, Nicholas Stephanopoulos, Ross Walton, Douglas S. Clark, and Matthew B. Francis

Langmuir 2010 Volume 26(Issue 22) pp:17383-17388

Publication Date(Web):October 21, 2010

DOI:10.1021/la1039305

We have developed a method for integrating the self-assembling tobacco mosaic virus capsid into hydrophobic solvents and hydrophobic polymers. The capsid was modified at tyrosine residues to display an array of linear poly(ethylene glycol) chains, allowing it to be transferred into chloroform. In a subsequent step, the capsids could be transferred to a variety of hydrophobic solvents, including benzyl alcohol, o-dichlorobenzene, and diglyme. The thermal stability of the material against denaturation increased from 70 °C in water to at least 160 °C in hydrophobic solvents. With a view toward material fabrication, the polymer-coated TMV rods were also incorporated into solid polystyrene and thermally cast at 110 °C. Overall, this process significantly expands the range of processing conditions for TMV-based materials, with the goal of incorporating these templated nanoscale systems into conductive polymer matrices.

Dual-Surface Modified Virus Capsids for Targeted Delivery of Photodynamic Agents to Cancer Cells

Co-reporter:Nicholas Stephanopoulos, Gary J. Tong, Sonny C. Hsiao, and Matthew B. Francis

ACS Nano 2010 Volume 4(Issue 10) pp:6014

Publication Date(Web):September 23, 2010

DOI:10.1021/nn1014769

Bacteriophage MS2 was used to construct a targeted, multivalent photodynamic therapy vehicle for the treatment of Jurkat leukemia T cells. The self-assembling spherical virus capsid was modified on the interior surface with up to 180 porphyrins capable of generating cytotoxic singlet oxygen upon illumination. The exterior of the capsid was modified with ∼20 copies of a Jurkat-specific aptamer using an oxidative coupling reaction targeting an unnatural amino acid. The capsids were able to target and selectively kill more than 76% of the Jurkat cells after only 20 min of illumination. Capsids modified with a control DNA strand did not target Jurkat cells, and capsids modified with the aptamer were found to be specific for Jurkat cells over U266 cells (a control B cell line). The doubly modified capsids were also able to kill Jurkat cells selectively even when mixed with erythrocytes, suggesting the possibility of using our system to target blood-borne cancers or other pathogens in the blood supply.Keywords: aptamers; photodynamic therapy; porphyrins; targeted delivery; viral capsids

Genome-Free Viral Capsids as Multivalent Carriers for Taxol Delivery

Co-reporter:Wesley Wu;SonnyC. Hsiao;ZacharyM. Carrico ;MatthewB. Francis

Angewandte Chemie 2009 Volume 121( Issue 50) pp:9657-9661

Publication Date(Web):

DOI:10.1002/ange.200902426

Nanoscale Integration of Sensitizing Chromophores and Porphyrins with Bacteriophage MS2

Co-reporter:Nicholas Stephanopoulos;ZacharyM. Carrico ;MatthewB. Francis

Angewandte Chemie International Edition 2009 Volume 48( Issue 50) pp:9498-9502

Publication Date(Web):

DOI:10.1002/anie.200902727

Genome-Free Viral Capsids as Multivalent Carriers for Taxol Delivery

Co-reporter:Wesley Wu;SonnyC. Hsiao;ZacharyM. Carrico ;MatthewB. Francis

Angewandte Chemie International Edition 2009 Volume 48( Issue 50) pp:9493-9497

Publication Date(Web):

DOI:10.1002/anie.200902426

Nanoscale Integration of Sensitizing Chromophores and Porphyrins with Bacteriophage MS2

Co-reporter:Nicholas Stephanopoulos;ZacharyM. Carrico ;MatthewB. Francis

Angewandte Chemie 2009 Volume 121( Issue 50) pp:9662-9666

Publication Date(Web):

DOI:10.1002/ange.200902727

Direct Cell Surface Modification with DNA for the Capture of Primary Cells and the Investigation of Myotube Formation on Defined Patterns

Co-reporter:Sonny C. Hsiao, Betty J. Shum, Hiroaki Onoe, Erik S. Douglas, Zev J. Gartner, Richard A. Mathies, Carolyn R. Bertozzi and Matthew B. Francis

Langmuir 2009 Volume 25(Issue 12) pp:6985-6991

Publication Date(Web):April 29, 2009

DOI:10.1021/la900150n

Previously, we reported a method for the attachment of living cells to surfaces through the hybridization of synthetic DNA strands attached to their plasma membrane. The oligonucleotides were introduced using metabolic carbohydrate engineering, which allowed reactive tailoring of the cell surface glycans for chemoselective bioconjugation. While this method is highly effective for cultured mammalian cells, we report here a significant improvement of this technique that allows the direct modification of cell surfaces with NHS−DNA conjugates. This method is rapid and efficient, allowing virtually any mammalian cell to be patterned on surfaces bearing complementary DNA in under 1 h. We demonstrate this technique using several types of cells that are generally incompatible with integrin-targeting approaches, including red blood cells and primary T-cells. Cardiac myoblasts were also captured. The immobilization procedure itself was found not to activate primary T-cells, in contrast to previously reported antibody- and lectin-based methods. Myoblast cells were patterned with high efficiency and remained undifferentiated after surface attachment. Upon changing to differentiation media, myotubes formed in the center of the patterned areas with an excellent degree of edge alignment. The availability of this new protocol greatly expands the applicability of the DNA-based attachment strategy for the generation of artificial tissues and the incorporation of living cells into device settings.

Oxidative coupling of peptides to a virus capsid containing unnatural amino acids

Co-reporter:Zachary M. Carrico, Dante W. Romanini, Ryan A. Mehl and Matthew B. Francis

Chemical Communications 2008 (Issue 10) pp:1205-1207

Publication Date(Web):29 Jan 2008

DOI:10.1039/B717826C

This Communication describes the chemo- and site-selective coupling of cell type-specific targeting peptides to a virus capsid containing aminophenylalanine residues.

Attachment of Peptide Building Blocks to Proteins Through Tyrosine Bioconjugation

Co-reporter:Dante W. Romanini and Matthew B. Francis

Bioconjugate Chemistry 2008 Volume 19(Issue 1) pp:153

Publication Date(Web):December 11, 2007

DOI:10.1021/bc700231v

Recent efforts have yielded a number of short peptide sequences with useful binding, sensing, and cellular uptake properties. In order to attach these sequences to tyrosine residues on intact proteins, a three-component Mannich-type strategy is reported. Two solid phase synthetic routes were developed to access peptides up to 20 residues in length with anilines at either the N- or C-termini. In the presence of 20 mM formaldehyde, these functional groups were coupled to tyrosine residues on proteins under mild reaction conditions. The identities of the resulting bioconjugates were confirmed using mass spectrometry and immunoblot analysis. Screening experiments have demonstrated that the method is compatible with substrates containing all of the amino acids, including lysine and cysteine residues. Importantly, tyrosine residues on proteins exhibit much faster reaction rates, allowing short peptides containing this residue to be coupled without cross reactions.

Energy Transfer Dynamics in Light-Harvesting Assemblies Templated by the Tobacco Mosaic Virus Coat Protein

Co-reporter:Ying-Zhong Ma, Rebekah A. Miller, Graham R. Fleming and Matthew B. Francis

The Journal of Physical Chemistry B 2008 Volume 112(Issue 22) pp:6887-6892

Publication Date(Web):May 10, 2008

DOI:10.1021/jp8006393

Picosecond time-resolved fluorescence spectroscopy was used to characterize energy transfer between chromophores displayed on a rod assembly of tobacco mosaic virus coat protein. The incorporation of donor chromophores with broad and overlapping absorption and emission spectra creates an “antenna” with a large absorption cross section, which can convey excitation energy over large distances before transfer to an acceptor chromophore. The possibility for both donor-to-donor and donor-to-acceptor transfer results in complex kinetic behavior at any single wavelength. Thus, to describe the various pathways of energy transfer within this system accurately, a global lifetime analysis was performed to obtain decay associated spectra. We found the energy transfer from donor to acceptor chromophores occurs in 187 ps with an efficiency of 36%. A faster decay component of 70 ps was also observed from global lifetime analysis and is attributed to donor-to-donor transfer. Although more efficient three-chromophore systems have been demonstrated, a two-chromophore system was studied here to facilitate analysis.

Protein-Cross-Linked Polymeric Materials through Site-Selective Bioconjugation

Co-reporter:AaronP. Esser-Kahn;MatthewB. Francis

Angewandte Chemie International Edition 2008 Volume 47( Issue 20) pp:3751-3754

Publication Date(Web):

DOI:10.1002/anie.200705564

DNA-Coated AFM Cantilevers for the Investigation of Cell Adhesion and the Patterning of Live Cells

Co-reporter:SonnyC. Hsiao;AileyK. Crow;WilburA. Lam;CarolynR. Bertozzi ;DanielA. Fletcher ;MatthewB. Francis

Angewandte Chemie International Edition 2008 Volume 47( Issue 44) pp:8473-8477

Publication Date(Web):

DOI:10.1002/anie.200802525

Protein-Cross-Linked Polymeric Materials through Site-Selective Bioconjugation

Co-reporter:AaronP. Esser-Kahn;MatthewB. Francis

Angewandte Chemie 2008 Volume 120( Issue 20) pp:3811-3814

Publication Date(Web):

DOI:10.1002/ange.200705564

N-Terminal Protein Modification through a Biomimetic Transamination Reaction

Co-reporter:JoshuaM. Gilmore;RebeccaA. Scheck; AaronP. Esser-Kahn;NeelS. Joshi ;MatthewB. Francis

Angewandte Chemie 2008 Volume 120( Issue 41) pp:

Publication Date(Web):

DOI:10.1002/ange.200890258

No abstract is available for this article.

DNA-Coated AFM Cantilevers for the Investigation of Cell Adhesion and the Patterning of Live Cells

Co-reporter:SonnyC. Hsiao;AileyK. Crow;WilburA. Lam;CarolynR. Bertozzi ;DanielA. Fletcher ;MatthewB. Francis

Angewandte Chemie 2008 Volume 120( Issue 44) pp:8601-8605

Publication Date(Web):

DOI:10.1002/ange.200802525

N-Terminal Protein Modification through a Biomimetic Transamination Reaction

Co-reporter:JoshuaM. Gilmore;RebeccaA. Scheck; AaronP. Esser-Kahn;NeelS. Joshi ;MatthewB. Francis

Angewandte Chemie International Edition 2008 Volume 47( Issue 41) pp:

Publication Date(Web):

DOI:10.1002/anie.200890204

No abstract is available for this article.

Genome-free Viral Capsids as Carriers for Positron Emission Tomography Radiolabels

Co-reporter:Dante W. Romanini;Jacob M. Hooker;Scott E. Taylor;Matthew B. Francis;James P. O’Neil

Molecular Imaging and Biology 2008 Volume 10( Issue 4) pp:

Publication Date(Web):2008/07/01

DOI:10.1007/s11307-008-0136-5

We have developed a modular synthetic strategy to append imaging agents to a viral capsid.The hollow protein shell of bacteriophage MS2 (mtMS2) was labeled on its inside surface with [18F]fluorobenzaldehyde through a multistep bioconjugation strategy. An aldehyde functional group was first attached to interior tyrosine residues through a diazonium coupling reaction. The aldehyde was further elaborated to an alkoxyamine functional group, which was then condensed with n.c.a. [18F]fluorobenzaldehyde. Biodistribution of the radioactive MS2 conjugates was subsequently evaluated in Sprague–Dawley rats.Relative to fluorobenzaldehyde, fluorine-18-labeled MS2 exhibited prolonged blood circulation time and a significantly altered excretion profile. It was also observed that additional small molecule cargo installed inside the capsids did not alter the biodistribution.These studies provide further insight into the pharmacokinetic behavior of nanomaterials and serve as a platform for the future development of targeted imaging and therapeutic agents based on mtMS2.

Self-assembled cellular microarrays patterned using DNA barcodes

Co-reporter:Erik S. Douglas, Ravi A. Chandra, Carolyn R. Bertozzi, Richard A. Mathies and Matthew B. Francis

Lab on a Chip 2007 vol. 7(Issue 11) pp:1442-1448

Publication Date(Web):19 Sep 2007

DOI:10.1039/B708666K

The successful integration of living cells into synthetic devices requires precise control over cell patterning. Here we describe a versatile platform that can accomplish this goal through DNA hybridization. Living cells functionalized with exogenous cell-surface DNA strands bind to cognate sequences of DNA printed on glass slides. Attachment via these “cell-adhesion barcodes” is rapid and specific, with close-packed arrays of cells forming within minutes. The biophysical properties of the system are characterized, and the technique is used to form complex cellular patterns with single-cell line widths and self-assembled cellular microarrays. Key advantages of DNA-directed cell binding include the ability to immobilize both adherent and non-adherent cells, to capture cells selectively from a mixed population, to tune the binding properties of the cells, and to reuse substrates prepared with widely available DNA printing technologies.

Regioselective Labeling of Antibodies through N-Terminal Transamination

Co-reporter:Rebecca A. Scheck and Matthew B. Francis

ACS Chemical Biology 2007 Volume 2(Issue 4) pp:247

Publication Date(Web):April 20, 2007

DOI:10.1021/cb6003959

A convenient new method is described for the introduction of ketone groups at the N-termini of antibodies. The reaction occurs in the presence of pyridoxal-5′-phosphate under conditions mild enough to maintain antigen binding function, as confirmed by enzyme-linked immunosorbent assay. Further derivatization of these functional sites was accomplished through oxime formation, yielding well-defined antibody conjugates for a wide range of applications. The ability of the modified antibodies to bind their targets was confirmed via immunodot blot analysis. The generality of this method has been demonstrated on a number of monoclonal and polyclonal antibodies, all with different binding specificities.

Chemical Biology at Berkeley

Co-reporter:Matthew B. Francis and Jamie H. Doudna Cate

ACS Chemical Biology 2007 Volume 2(Issue 11) pp:702

Publication Date(Web):November 16, 2007

DOI:10.1021/cb700215c

Integration of a Self-Assembling Protein Scaffold with Water-Soluble Single-Walled Carbon Nanotubes

Co-reporter:Patrick G. Holder;Matthew B. Francis

Angewandte Chemie 2007 Volume 119(Issue 23) pp:

Publication Date(Web):25 APR 2007

DOI:10.1002/ange.200700333

Plastikrohre: Das parallele Ausrichten von einwandigen Kohlenstoffnanoröhren (NTs) und einem selbstorganisierenden Biomolekülgerüst, dem Tabakmosaikvirus (TMV), gelingt mithilfe eines multifunktionellen polymeren Tensids: Die NTs werden durch Umhüllen mit einer Polyethylenglycol-Schicht solubilisiert, die über einen Pyrenanker angebunden ist, und die endständigen Alkoxyamingruppen des Tensids ermöglichen eine milde Biokonjugation mit Keton-markierten Proteinen.

Integration of a Self-Assembling Protein Scaffold with Water-Soluble Single-Walled Carbon Nanotubes

Co-reporter:Patrick G. Holder;Matthew B. Francis

Angewandte Chemie International Edition 2007 Volume 46(Issue 23) pp:

Publication Date(Web):25 APR 2007

DOI:10.1002/anie.200700333

Plastic tubing: The parallel alignment of single-walled carbon nanotubes (NTs) with a self-assembling biomolecular scaffold, the tobacco mosaic virus (TMV), is presented. A multifunctional polymeric surfactant brings together these two disparate components: The NTs are solubilized by a layer of poly(ethylene glycol) attached through a pyrene anchor, and the pendant alkoxyamine groups of the surfactant allow mild bioconjugation with ketone-labeled proteins.

Transition metal catalyzed methods for site-selective protein modification

Co-reporter:John M Antos, Matthew B Francis

Current Opinion in Chemical Biology 2006 Volume 10(Issue 3) pp:253-262

Publication Date(Web):June 2006

DOI:10.1016/j.cbpa.2006.04.009

The broad utility of protein bioconjugates has created a need for new and diverse strategies for site-selective protein modification. In particular, chemical reactions that target alternative amino acid side chains or unnatural functional groups are emerging as a valuable complement to more commonly used lysine- and cysteine-based strategies. Considering their widespread use in organic synthesis, reactions catalyzed by transition metals could provide a particularly powerful set of transformations for the continued expansion of the bioconjugation toolkit. Recent efforts to apply transition metal catalysis to protein modification have resulted in new methods for protein cross-linking, tryptophan modification, tyrosine modification, reductive amination of protein amines, and unnatural amino acid labeling. These strategies have substantially expanded the synthetic flexibility of protein modification, and thus the range of applications for which bioconjugates can be used in chemical biology and materials science.

N-Terminal Protein Modification through a Biomimetic Transamination Reaction

Co-reporter:Joshua M. Gilmore;Rebecca A. Scheck;Aaron P. Esser-Kahn;Neel S. Joshi

Angewandte Chemie 2006 Volume 118(Issue 32) pp:

Publication Date(Web):17 JUL 2006

DOI:10.1002/ange.200600368

Unter milden Bedingungen gelingt die hier vorgestellte biomimetische Transaminierung, die Pyridoxal-5-phosphat nutzt, um den N-Terminus von Proteinen und Peptiden zu modifizieren. Dabei wird eine einzigartig reaktive Carbonylgruppe an einer einzigen Stelle eingeführt (siehe Schema), die als Ausgangsstelle für eine Oxim- oder Hydrazonbildung dienen kann. Die Modifizierungsstrategie eignet sich auch für Proteine, die freie Cysteinreste enthalten.

Programmable Cell Adhesion Encoded by DNA Hybridization

Co-reporter:Ravi A. Chra;Erik S. Douglas;Richard A. Mathies ;Carolyn R. Bertozzi

Angewandte Chemie 2006 Volume 118(Issue 6) pp:

Publication Date(Web):21 DEC 2005

DOI:10.1002/ange.200502421

Angeklebte Gene: Lebende Zellen, die mit Einzelstrang-DNA-Oligonucleotiden funktionalisiert sind, binden – unabhängig von nativen Adhäsionsmechanismen – sequenzspezifisch an Substrate mit komplementären DNA-Strängen. Diese Strategie erwies sich bei einer Reihe gängiger Säugerzelllinien und Funktionseinheiten als erfolgreich.

N-Terminal Protein Modification through a Biomimetic Transamination Reaction

Co-reporter:Joshua M. Gilmore;Rebecca A. Scheck;Aaron P. Esser-Kahn;Neel S. Joshi

Angewandte Chemie International Edition 2006 Volume 45(Issue 32) pp:

Publication Date(Web):17 JUL 2006

DOI:10.1002/anie.200600368

One hit wonder: A biomimetic transamination reaction has been developed that employs pyridoxal-5-phosphate to modify the N terminus of proteins and peptides under mild conditions. This technique introduces a uniquely reactive carbonyl group in a single location (see scheme), thus allowing further elaboration through oxime or hydrazone formation. This modification strategy is also compatible with proteins containing a free cysteine residue.

Programmable Cell Adhesion Encoded by DNA Hybridization

Co-reporter:Ravi A. Chandra, Erik S. Douglas, Richard A. Mathies, Carolyn R. Bertozzi,Matthew B. Francis

Angewandte Chemie International Edition 2006 45(6) pp:896-901

Publication Date(Web):

DOI:10.1002/anie.200502421

Oxidative coupling of peptides to a virus capsid containing unnatural amino acids

Co-reporter:Zachary M. Carrico, Dante W. Romanini, Ryan A. Mehl and Matthew B. Francis

Chemical Communications 2008(Issue 10) pp:NaN1207-1207

Publication Date(Web):2008/01/29

DOI:10.1039/B717826C

This Communication describes the chemo- and site-selective coupling of cell type-specific targeting peptides to a virus capsid containing aminophenylalanine residues.