Stephen B.H. Kent
Research Summary / Selected Publications
We apply the tools of chemistry to elucidate the molecular basis of the biological functions of proteins. Ultimately we want to be able to design and build protein molecules with pre-determined, controlled properties. This is a scientific problem of great timeliness with the completion of the genome sequencing projects, which impact broadly across the natural sciences.
In the post-genome era it will be imperative to understand the principles that govern the numerous and diverse activities of proteins in the biological world. These principles can best be elucidated by combining a number of scientific disciplines. To that end, we have established general synthetic access to the world of proteins. This enables us to focus the most advanced physical and chemical techniques in conjunction with all the tools of molecular biology to elucidate the molecular basis of the biochemical and biological actions of the protein molecule.
The emphasis in our research program is on collaborative science. This creates unique opportunities for people drawn to the application of chemistry to biological systems. Thus, techniques such as Xray crystallography, nuclear magnetic resonance (NMR), and Fourier-transform infrared (FTIR) spectroscopy can be applied to protein systems that have been labeled in a non-perturbing fashion with probe nuclei to act as local reporter groups. This enables the fruitful application of these powerful methods to complex protein systems. Synthetic organic and peptidomimetic chemistry can also be used to systematically dissect the molecular basis of enzyme activity by varying the covalent structure of a protein in a completely general yet controlled fashion, and correlating these precise changes with effects on protein function.
We apply the tools of chemistry to elucidate the molecular basis of the biological functions of proteins. Ultimately we want to be able to design and build protein molecules with pre-determined, controlled properties. This is a scientific problem of great timeliness with the completion of the genome sequencing projects, which impact broadly across the natural sciences.
In the post-genome era it will be imperative to understand the principles that govern the numerous and diverse activities of proteins in the biological world. These principles can best be elucidated by combining a number of scientific disciplines. To that end, we have established general synthetic access to the world of proteins. This enables us to focus the most advanced physical and chemical techniques in conjunction with all the tools of molecular biology to elucidate the molecular basis of the biochemical and biological actions of the protein molecule.
The emphasis in our research program is on collaborative science. This creates unique opportunities for people drawn to the application of chemistry to biological systems. Thus, techniques such as Xray crystallography, nuclear magnetic resonance (NMR), and Fourier-transform infrared (FTIR) spectroscopy can be applied to protein systems that have been labeled in a non-perturbing fashion with probe nuclei...
Thomas Durek, Vladimir Yu. Torbeev, Stephen B. H. Kent, "Convergent chemical synthesis and high resolution X-ray structure of human lysozyme." Proc. Natl. Acad. Sci. USA, 104, 4846-4851 (2007)
Dissecting the energetics of protein -helix C-cap termination through chemical protein synthesis.
Duhee Bang, Alexey V. Gribenko, Valentina Tereshko, Anthony A. Kossiakoff, Stephen B. Kent*, George I. Makhatadze*,
Nature Chemical Biology, 2, 139-143 (2006)
A one-pot chemical synthesis of Crambin.
Duhee Bang, Stephen B.H. Kent,
Angew. Chem. Int. Ed. Eng. 116: 2588-2592 (2004).
Design and chemical synthesis of a homogeneous polymer-modified erythropoiesis protein.
Gerd G. Kochendoerfer, Shiah-Yun Chen, Feng Mao, Sonya Cressman, Stacey Traviglia, Haiyan Shao, Christie Hunter, Don Low, Neil Cagle, Maia Carnevali, Vincent Gueriguian, Peter Keogh, Heather Porter, Stephen M. Stratton, M. Con Wiedeke, Jill Wilken, Jie Tang, Jay J. Levy, Les P. Miranda, Milan Crnogorac, Suresh Kalbag, Paolo Botti, Janice Schindler-Horvath, Laura Savatski, John W. Adamson, Ada Kung, Stephen B. H. Kent, James A. Bradburne,
Science 299: 884-887 (2003)
Total synthesis of cytochrome b562 by native chemical ligation using a removable auxiliary.
D.W. Low, M.G. Hill, M.R. Carrasco, P. Botti, S.B. Kent,
Proc. Nat. Acad. Sci. USA 98: 6554-9 (2001)
Total chemical synthesis of the integral membrane protein influenza A virus M2 proton channel: role of its cytoplasmic domain for pore assembly.
Gerd G. Kochendoerfer, David Salom, James D. Lear, Stephen B. H. Kent, William F. DeGrado,
Biochemistry 38: 11905-13 (1999).
Ionization states of the catalytic residues in HIV-1 Protease.
Ross Smith, Ian M. Brereton, Richard Y. Chai, Stephen B. H. Kent,
Nature Structural Biology 3: 946-950 (1996).
Thomas Durek, Vladimir Yu. Torbeev, Stephen B. H. Kent, "Convergent chemical synthesis and high resolution X-ray structure of human lysozyme." Proc. Natl. Acad. Sci. USA, 104, 4846-4851 (2007)
Dissecting the energetics of protein -helix C-cap termination through chemical protein synthesis.
Duhee Bang, Alexey V. Gribenko, Valentina Tereshko, Anthony A. Kossiakoff, Stephen B. Kent*, George I. Makhatadze*,
Nature Chemical Biology, 2, 139-143 (2006)
A one-pot chemical synthesis of Crambin.
Duhee Bang, Stephen B.H. Kent,
Angew. Chem. Int. Ed. Eng. 116: 2588-2592 (2004).
Design and chemical synthesis of a homogeneous polymer-modified erythropoiesis protein.
Gerd G. Kochendoerfer, Shiah-Yun Chen, Feng Mao, Sonya Cressman, Stacey Traviglia, Haiyan Shao, Christie Hunter, Don Low, Neil Cagle, Maia Carnevali, Vincent Gueriguian, Peter Keogh, Heather Porter, Stephen M. Stratton, M. Con Wiedeke, Jill Wilken, Jie Tang, Jay J. Levy, Les P. Miranda, Milan Crnogorac, Suresh Kalbag, Paolo Botti, Janice Schindler-Horvath, Laura Savatski, John W. Adamson, Ada Kung, Stephen B. H. Kent, James A. Bradburne,
Science 299: 884-887 (2003)
Total synthesis of cytochrome b562 by native chemical ligation using a removable auxiliary.
D.W. Low, M.G. Hill, M.R. Carrasco, P. Botti, S.B. Kent,
Proc. Nat. Acad. Sci. USA 98: 6554-9 (2001)
