Henry Dube

 

PhD Student

Location:

HCI G-328

Phone:

+41-1-633 4181

e-mail:

Henry Dube

Education

1998-2004:

Study of chemistry at Philipps-University in Marburg and at LMU in Munich

2001:

Internship at the Russian Academy of Science in Moscow

2002:

Internhip at Hoffmann-La Roche in Basel

2003-2004:

Diploma thesis with Prof. P. Knochel at LMU in Munich

since 2004:

PhD with Prof. F. Diederich at ETH Zurich

Dendridic Modell Compounds for Hemoglobin and Myoglobin

Myoglobin and hemoglobin from different vertebrates show very similar structural features at their oxygen binding sites. Besides the so-called “proximal” histidine, which helps to stabilize the heme group in the protein pocket and plays a crucial role for the cooperative binding of oxygen in hemoglobin, the so-called “distal” histidine is also strongly conserved in the proteins. There is much ongoing debate about the influence of this histidine on fine-tuning the CO and O2 binding affinities of the proteins. Discrimination between these two ligands is essential for aerobic organisms to ensure sufficient oxygen supply. It is argued whether the distal histidine interacts sterically with CO and destabilizes the CO-adduct, or interacts via an H-bond with O2 and stabilizes the O2-adduct.


Overlay of the active sites of the a-subunit of human hemoglobin (grey) and sperm whale myoglobin (green)

In the group of Prof. Diederich a series of dendritic model compounds for myoglobin and hemoglobin were already synthesized. One example is given in the picture below. The oxygen binding affinity of these systems reached up to 1500 times that of the native proteins.
The task of this thesis is the synthesis of a related but more elaborate model compound, which includes a distal H-bond donor, to probe the influence of a possible H-bond on the oxygen binding affinity in this model system.


Dendritic model compound for hemoglobin and myoglobin from the Diederich group

Publications

I. Sapountzis, H. Dube, R. Lewis, N. Gommermann, P. Knochel, J. Org. Chem. 2005, 2015-2025. Synthesis of Chiral a-Aminoalkylpyrimidines 70, 2445-2454. Synthesis of Functionalized Nitroarylmagnesium Halides via an Iodine-Magnesium Exchange.

H. Dube, N. Gommermann, P. Knochel, Synthesis 2004, 2015-2025. Synthesis of Chiral a-Aminoalkylpyrimidines Using an Enantioselective Three-Component Reaction.

I. Sapountzis, H. Dube, P. Knochel, Adv. Syn. Catal. 2004, 346, 709-712. Synthesis of Nitro-Substituted Polyfunctional Biphenyls by Negishi Cross-Coupling of o-Nitroarylzinc Reagents.