Fraser Hof

 

Postdoctoral Fellow

Location:

HCI G-304

Phone:

+41-1-633 4172

e-mail:

Fraser Hof

Education

1993-1998:

B.Sc. in chemistry, University of Alberta, Edmonton, Canada

1998-2003:

Ph.D. in chemistry, The Scripps Research Institute with Prof. Julius Rebek, Jr.

2003-2004:

Novartis Foundation post-doctoral fellow with Prof. F. Diederich at ETH Zurich

2004-present:

Human Frontier Science Program post-doctoral fellow with Prof. F. Diederich at ETH Zurich

A Weak, Attractive Interaction Between Organic Fluorine and an Amide

with Denise M. Scofield

A "molecular torsion balance" used to measure weak fluorine---amide interactions

Recent results have suggested that an attraction between organic fluorine and the face of an amide may be operative in enzyme-inhibitor interactions. We have applied a combination of a chemical double-mutant cycle and a linear free energy relationship to a model system in order to demonstrate that a weak attractive interaction (–0.8 to –1.5 kJ mol –1) exists between organic fluorine and the face of an amide functional group.

New Nonpeptidic Inhibitors of the Malarial Protease Plasmepsin II

with Andri Schütz

Molecular model of a plasmepsin II inhibitor (right) docked into the enzyme's active site

Malaria is the most prolific infectious disease in the world, infecting up to 500 million people annually. Plasmepsin II is a malarial aspartyl protease that has been proposed as a new therapeutic target that will overcome the growing incidence of drug resistant parasites. We have designed a new family of plasmepsin II inhibitors that aim to: 1) bind to the catalytic aspartate dyad (red) using a novel bicyclic ammonium core, 2) engage the shallow S1/S3 cleft (orange) with an aromatic substituent, and 3) target a hydrophobic substituent for binding in the deep flap pocket (yellow) that opens when the enzyme undergoes an induced conformational shift.

Publications

F. Hof, D. M. Scofield, W. B. Schweizer, F. Diederich, Angew. Chem. Int. Ed. 2004, in press. A Weak Attractive Interaction Between Organic Fluorine and an Amide.

F. Hof, F. Diederich, Chem. Commun. 2004, 5, 484-487. Medicinal Chemistry in Academia: Molecular Recognition with Biological Receptors.

S. M. Biros, E. C. Ullrich, F. Hof, L. Trembleau, J. Rebek, Jr., J. Am. Chem. Soc. 2004, 126, 2870-2874. Molecular Recognition in Water: The Role of Hydration and Hydrophilicity in Guest Selection.

D. W. Johnson, F. Hof, L. C. Palmer, T. Martín, U. Obst, J. Rebek, Jr., Chem. Commun. 2003, 1638-1639. Glycoluril Ribbons Tethered by Complementary Hydrogen Bonds.

F. Hof, L. Trembleau, E. C. Ullrich, J. Rebek, Jr., Angew. Chem. Int. Ed. 2003, 42, 3150-3153. Acetylcholine Recognition by a Deep, Biomimetic Pocket.

D. W. Johnson, F. Hof, P. M. Iovine, C. Nuckolls, J. Rebek, Jr., Angew. Chem. Int. Ed. 2002, 41, 3793-3796. Solid State and Solution Studies of a Tetrameric Hydrogen-Bonded Capsule and its Guests.

D. W. Johnson, L. C. Palmer, F. Hof, P. M. Iovine, J. Rebek, Jr., Chem. Commun. 2002, 2228-2229. New Supramolecular Organization for Glycoluril: Chiral Hydrogen-Bonded Ribbons.

F. Hof, S. L. Craig, C. Nuckolls, J. Rebek, Jr., Angew. Chem. Int. Ed. 2002, 41, 1488-1508. Molecular Encapsulation.

F. Hof, J. Rebek, Jr., Proc. Nat. Acad. Sci. U.S.A. 2002, 99, 4775-4777. Molecules-Within-Molecules: Molecular Recognition Through Self-Assembly.

F. Hof, P. M. Iovine, D. W. Johnson, J. Rebek, Jr., Org. Lett. 2001, 3, 4247-4249. Highly Selective Synthesis of Heterosubstituted Aromatic Sulfamides

F. Hof, L. C. Palmer, J. Rebek, Jr., J. Chem. Ed. 2001, 78, 1519-1524. Synthesis and Self-Assembly of the "Tennis Ball" Dimer and Subsequent Encapsulation of Methane: An Advanced Organic Chemistry Laboratory Experiment.

F. Hof, C. Nuckolls, S. L. Craig, T. Martín, J. Rebek, Jr., , J. Am. Chem. Soc. 2000, 122, 10991-10996. Emergent Conformational Preferences of a Self-Assembling Small Molecule: Structure and Dynamics in a Tetrameric Capsule.

F. Hof, C. Nuckolls, J. Rebek, Jr., J. Am. Chem. Soc. 2000, 122, 4251-4252. Diversity and Selection in Self-Assembled Tetrameric Capsules.

C. Nuckolls, F. Hof, T. Martín, J. Rebek, Jr., J. Am. Chem. Soc. 1999, 121, 10281-10285. Chiral Microenvironments in Self-Assembled Capsules.

M. M. M. Pelisson, G. V. J. da Silva, D. L. J. Clive, D. M. Coltart, F. A. Hof, J. Het. Chem. 1999, 36, 653-658. Studies on the Preparation of 3,4-Disubstituted 2-Methoxypyridines.