Willi Amberg

Bio: Willi Amberg is an academic researcher from Scripps Research Institute. The author has contributed to research in topics: Dihydroxylation & Medicine. The author has an hindex of 6, co-authored 8 publications receiving 1924 citations. Previous affiliations of Willi Amberg include Massachusetts Institute of Technology.

The Osmium-Catalyzed Asymmetric Dihydroxylation: A New Ligand Class and a Process Improvement

Abstract: Two key improvements in the osmiuun-catalyzed asymmetric dihydroxylation have led to a simple procedure which is applicable to a wide range of olefins.

New ligands double the scope of the catalytic asymmetric dihydroxylation of olefins

Abstract: Improved ligands render terminal olefins good substrates for the osmium-catalyzed asymmetric dihydroxylation (ADH) process, and the amounts of chiral ligand and osmium catalyst required diminish dramatically

Syntheses and crystal structures of the cinchona alkaloid derivatives used as ligands in the osmium-catalyzed asymmetric dihydroxylation of olefins

Abstract: Experimental procedures for the preparation of two classes of derivatives of the cinchona alkaloids dihydroquinine and dihydroquinidine are described. Ligands (DHQ) 2 -PHAL, 1a, and (DHQD) 2 -PHAL, 2a, are conveniently synthesized in good yield by the reaction of the corresponding alkaloid with 1,4-dichlorophthalazine in the presence of K 2 CO 3 and KOH in refluxing toluene. Derivatives DHQ-PHN, 1b, and DHQD-PHN, 2b, are prepared through an Ullmann-type coupling between the 9-O-alkaloid sodium alkoxide and 9-iodophenanthrene in the presence of CuI and pyridine. Crystal structures for derivatives 2a and 2b are also presented. These four alkaloid derivatives serve as highly enantioselective ligands for the osmium tetraoxide catalyzed asymmetric dihydroxylation (AD) of olefins

Copper-mediated coupling reactions and their applications in natural products and designed biomolecules synthesis.

Abstract: 6.4. Polyynes 3123 6.5. Using R-Hydroxy Stannanes 3124 6.6. Using the Hurtley Reaction 3124 6.7. Using a Methylenation Reaction 3125 7. Conclusions and Future Prospects 3125 8. Uncommon Abbreviations 3125 9. Acknowledgments 3125 10. Note Added in Proof 3125 11. References 3126 * Authorstowhomcorrespondenceshouldbeaddressed(evano@chimie.uvsq.fr, nicolas.blanchard@uha.fr). † Université de Versailles Saint Quentin en Yvelines. ‡ Université de Haute-Alsace. Chem. Rev. 2008, 108, 3054–3131 3054

Human antibodies with sub-nanomolar affinities isolated from a large non-immunized phage display library.

Abstract: To generate a stable resource from which high affinity human antibodies to any given antigen can be rapidly isolated, functional V-gene segments from 43 non-immunized human donors were used to construct a repertoire of 1.4 x 10(10) single-chain Fv (scFv) fragments displayed on the surface of phage. Fragments were cloned in a phagemid vector, enabling both phage displayed and soluble scFv to be produced without subcloning. A hexahistidine tag has been incorporated to allow rapid purification of scFv by nickel chelate chromatography. This library format reduces the time needed to isolate monoclonal antibody fragments to under two weeks. All of the measured binding affinities show a Kd < 10 nM and off-rates of 10(-3) to 10(-4) s-1, properties usually associated with antibodies from a secondary immune response. The best of these scFvs, an anti-fluorescein antibody (0.3 nM) and an antibody directed against the hapten DTPA (0.8 nM), are the first antibodies with subnanomolar binding affinities to be isolated from a naive library. Antibodies to doxorubicin, which is both immunosuppressive and toxic, as well as a high affinity and high specificity antibody to the steroid hormone oestradiol have been isolated. This work shows that conventional hybridoma technology may be superseded by large phage libraries that are proving to be a stable and reliable source of specific, high affinity human monoclonal antibodies.

Isolation of high affinity human antibodies directly from large synthetic repertoires.

Abstract: Antibody fragments of moderate affinity (approximately microM) can be isolated from repertoires of approximately 10(8) immunoglobulin genes by phage display and rounds of selection with antigen, and the affinities improved by further rounds of mutation and selection. Here, as an alternative strategy, we attempted to isolate high affinity human antibodies directly from large repertoires. We first created highly diverse repertoires of heavy and light chains entirely in vitro from a bank of human V gene segments and then, by recombination of the repertoires in bacteria, generated a large (close to 6.5 x 10(10)) synthetic repertoire of Fab fragments displayed on filamentous phage. From this repertoire we isolated Fab fragments which bound to a range of different antigens and haptens, and with affinities comparable with those of antibodies from a secondary immune response in mice (up to 4 nM). Although the VH-26 (DP-47) segment was the most commonly used segment in both artificial and natural repertoires, there were also major differences in the pattern of segment usage. Such comparisons may help dissect the contributions of biological mechanisms and structural features governing V gene usage in vivo.

Efficient neutralization of primary isolates of HIV-1 by a recombinant human monoclonal antibody

Abstract: The ability of antibodies to neutralize diverse primary isolates of human immunodeficiency virus-type 1 in vitro has been questioned, with implications for the likely efficacy of vaccines. A recombinant human antibody to envelope glycoprotein gp120 was generated and used to show that primary isolates are not refractory to antibody neutralization. The recombinant antibody neutralized more than 75 percent of the primary isolates tested at concentrations that could be achieved by passive immunization, for example, to interrupt maternal-fetal transmission of virus. The broad specificity and efficacy of the antibody implies the conservation of a structural feature on gp120, which could be important in vaccine design.