Robert S. Hodges, Ph.D., F.R.S.C.
Professor of Biochemistry & Molecular
Genetics
Director of the Program in Biomolecular Structure
John Stewart Endowed Chair in Peptide Chemistry
Department of Biochemistry and Molecular
Genetics
University of Colorado at Denver and Health Sciences Center
RC1 South Tower, Room 9121
P.O. Box 6511 MS 8101
Aurora, Colorado 80045
Office Phone: 303.724-3253
Lab Phone: 303.724-3252
Fax: 303.724-3249
Assistant: Jackie Newnam 303 724-3268
Robert.Hodges@uchsc.edu
EDUCATION/EXPERIENCE
HONORS AND AWARDS
PROFESSIONAL ACTIVITIES
LAB PERSONNEL
Research Interests
Synthetic peptide
and antipeptide approaches play major roles in understanding protein
structure and function. Our research interests range from:
1) The de novo design of model proteins, an important endeavor
that not only tests our understanding of protein folding and structure
but also lays the groundwork for the design of novel proteins with
the desired biological/immunological activities. We have selected
the two-stranded a-helical coiled-coil
as an ideal model system for studying protein stability, subunit
interactions and protein folding. In addition, we are studying native
coiled-coils in tropomyosin, the transporter protein ProP and in
the motor proteins, kinesin and kinesin-like proteins, dynein and
dynamin;
2) Our expertise in understanding the formation and stability of
coiled-coils has resulted in a new project to investigate the coiled-coil
domains in the SARS (Severe Acute Respiratory Syndrome) coronavirus
spike glycoprotein. The aim is to design and synthesize stable peptides
and peptidomimetics that will inhibit SARS virus infection of human
cells;
3) The design and engineering of peptides for biotechnology applications.
This area includes the development of novel antimicrobial cyclic
peptides with enhanced antimicrobial activity, low toxicity with
broad spectrum activity or activity profiles for selected clinical
indications. The development of a novel peptidylmimetic as a therapeutic
to treat Pseudomonas aeruginosa. The design of comformationally
defined and constrained combinatorial peptide libraries for drug
discovery. The de novo design of templates to prepare antibodies
that recognize a-helical protein sequences
in native proteins;
4) The development of synthetic peptide anti-adhesin bacterial
vaccines and antibody therapeutics. These antigen-antibody studies
will also investigate such issues as strain-specificity, cross-reactivity,
and immunogen presentation as a peptide versus the same region presented
in the native protein, which will lead to a better understanding
of the immune response at the molecular level;
5) The development of novel HPLC and capillary electrophoretic
methods for the separation of peptides and proteins for proteomic
applications. Our goal is to replace two-dimensional gel electrophoresis
with two-dimensional chromatography or a combined chromatography/capillary
electrophoresis method prior to MS/MS. In addition, we will continue
our studies to demonstrate the general feasibility of equating polypeptide
reversed-phase chromatography (RPC) elution behavior with peptide
and protein stability, conformation and function. Of particular
significance is our recent introduction of "temperature profiling"
in RPC which enables a highly sensitive monitoring of the association
of peptide molecules either through oligomerization or aggregation;
6) The above projects involve a wide range of technologies in
protein chemistry: peptide synthesis, HPLC, CE, amino acid analysis,
mass spectrometry and characterization of peptides and proteins
by CD and NMR spectroscopy, analytical ultracentrifugation, Biacore
analysis and a range of bioassays.
Selected Publications
-
Tripet, B., D. Kao, S. Jeffers, K. Holmes and R.S. Hodges.
Template-based Coiled-coil antigens elicit neutralizing antibodies
to the SARS-Coronavirus. J. Structural Biology 155: 176-194
(2006).
-
Chen, Y., A.I. Vasil, L. Rehaume, C.T. Mant, J.L. Burns, M.L.
Vasil, R.E.W. Hancock, R.S. Hodges. Comparison of biophysical
and biological properties of -helical enantiomeric antimicrobial
peptides. Chemical Biology and Drug Design 67: 162-173 (2006).
-
Kovacs, J.M., C.T. Mant and R.S. Hodges. Determination of the
intrinsic hydrophilicity/hydrophobicity of amino acid side-chains
in peptides in the absence of Nearest-Neighbor or Conformational
Effects. Peptide Science (Biopolymers) 84: 298-309 (2006).
-
Chen, Y., C.T. Mant, S.W. Farmer, R.E.W. Hancock, M.L. Vasil
and R.S. Hodges. Rational design of -helical antimicrobial peptides
with enhanced activities and specificity/therapeutic index.
J. Biol. Chem. 280: 12316-12329 (2005).
-
Kwok, S.C. and R.S. Hodges. Stabilizing and Destabilizing Clusters
in the Hydrophobic Core of Long Two-stranded -Helical Coiled-Coils.
J. Biol. Chem. 279: 21576-21588 (2004).
-
Cachia, P.J., D.J. Kao and R.S. Hodges. Synthetic peptide vaccine
development: Measurement of polyclonal antibody affinity and
cross-reactivity using a new peptide capture and release system
for surface plasmon resonance spectroscopy. J. Mol. Recognition
17: 540-557 (2004).
-
Tripet, B., M.W. Howard, M. Jobling, R.K. Holmes, K.V. Holmes,
and R.S. Hodges. Structural characterization of the SARS-Coronavirus
Spike Fusion Protein Core. J. Biol. Chem. 279: 20836-20849 (2004).
- Zoetewey, D.L., B. Tripet, T. Kutateladze, M. Overduin, J.M.
Wood and R.S. Hodges. NMR solution
structure of the cytoplasmic antiparallel coiled-coil domain from
Escherichia coli ProP. J. Mol. Biol 334:1063-1076 (2003).
-
Lee, D.L., S. Ivaninskii, P. Burkhard and R.S.
Hodges. Unique stabilizing interactions identified in
the two-stranded alpha-helical coiled-coil: crystal structure
of a cortexillin I/GCN4 hybrid coiled-coil peptide. Protein
Sci. 12:1395-1405 (2003).
-
Lee, D.L. and R.S. Hodges.
Structure-activity relationships of de novo designed cyclic
antimicrobial peptides based on Gramicidin S. Biopolymers (Peptide
Science) 71:28-48 (2003).
Bibliography
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