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Edward Arnold
Professor
Rutgers
University
Chemistry & Chemical Biology
CABM
Room 016
679 Hoes Lane
Piscataway. N. J. 08854
(732) 235-5323
FAX - 5788
arnold@cabm.rutgers.edu |
HIV. AIDS. drugs. vaccines. crystallography. structural biology
Drs. Eddy and Gail Ferstandig Arnold and
their colleagues are working to develop and apply structure-based drug and
vaccine designs for the treatment and prevention of serious human
diseases. In pursuit of these goals. their laboratory takes advantage of
cutting-edge research tools. including X-ray crystallography. molecular
biology. virology. protein biochemistry. and macromolecular engineering.
The approaches being developed in the
Arnold laboratory are broadly applicable to a wide array of human health
problems. ranging from infectious diseases to cancer and diseases caused
by hereditary genetic defects. Much of the Arnold lab's research effort
to date has focused on the development of drugs and vaccines for the
treatment of AIDS. Examples of the results of these studies include: 1)
collaborative development of potential drugs for the treatment of AIDS. some of which may be more effective than treatments in current use; and 2)
production of AIDS vaccine candidates that have elicited protective immune
responses against HIV.
Dr. Arnold studies reverse transcriptase
(RT). which is an essential component of the AIDS virus and the target of
many of the most widely used anti-AIDS drugs. Using the techniques of
X-ray crystallography. his team has solved the three-dimensional
structures of HIV-1 RT in complex with antiviral drugs and pieces of the
HIV genome. These studies have illuminated the working of an intricate and
fascinating biological machine in atom-by-atom detail and have yielded
numerous novel insights into polymerase structure-function relationships. detailed mechanisms of drug resistance. and structure-based design of RT
inhibitors. Synthesis of the information being developed has lead to the
development of inhibitors that show great promise as potential treatments
for AIDS.
Another major project in his laboratory. co-directed by Dr. Gail Ferstandig Arnold. consists of engineering of a
human common cold virus. rhinovirus. to display appropriate segments from
more dangerous pathogens for the purpose of developing vaccines against
these pathogens. This work involves generating large numbers of chimeric
human rhinoviruses using a technique called random systematic mutagenesis.
With this method. the foreign sequences are linked to the HRV sequences
via adapters of randomized sequences and lengths. leading to a large array
of presentations. Large sets of such viruses are generated and selected to
optimize the isolation of vaccine candidates with the most effectively
reconstructed foreign segments. Constructs have been made that elicit
antibodies (in guinea pigs) capable of potently neutralizing the AIDS
virus in cell culture. His team is also analyzing the structures of some
of the engineered viruses using X-ray crystallography. with the long-term
objectives of determining three-dimensional correlates of immunogenicity
and developing a structural basis for design of more effective human
vaccines.
The Arnold group will continue to study
medically important problems using basic scientific tools and approaches.
In addition to potentially developing novel vaccines and chemotherapeutic
agents. the laboratory aims to gain greater insights into the basic
molecular processes of living systems.
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Ribbons representation
of the structure of HIV-1 RT in complex with the polypurine RNA:DNA.
The fingers. palm. thumb. connection. and RNase H subdomains of p66
are colored blue. red. green. yellow. and orange. respectively. The
p51 subunit is colored gray. The RNA template and DNA primer strands
are shown in blue and magenta. respectively. |
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