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Disintegrins are
non-enzymatic proteins produced in the venoms of snakes.
These proteins are characterized by their small size (7-11 KDa),
a repeated number of cysteines (characteristic of their protein
family), and a binding loop which binds to integrin receptors on
many cell types. Many of the identified disintegrins contain an
RGD in their binding loop that allows them to compete with the
native physiological ligand (for example: fibronectic,
vitronectin, collagen). Disintegrins with an RGD motif bind to
blood platelets and block coagulation. Others can bind to
cancer cells, induce apoptosis, block metastasis, angiogenesis
and proliferation. Due to these properties, disintegrins
make excellent candidates for the development of anti-cancer
therapies.
I have an active
collaboration with the Natural Toxin Research Center (NTRC) at
Texas A&M University. In the past three years we have
identified several disintegrins with potential biomedical
applications. My lab has also cloned several of these
disintegrin genes and we are now in the process of expressing
these and determining their biological activity.
Proposed Undergraduate Role in the
Investigation
Undergraduate students
participating in RUMBA will serve a vital role in this
investigation.
RUMBA students will have the opportunity
to develop and test their own ideas within the framework of this
research. Examples of possible projects students
can become interested in investigating are: a) isolation of
novel disintegrin genes using RT-PCR, cloning and expression of
those genes, b) producing specific mutations in the RGD binding
loop and predicting activity using protein modeling programs, and c)
examining genomic structure of ADAM genes.
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Dr. Soto (left) with one of his
graduate students.
We are interested in identifying
disintegrin genes that when expressed their protein products can
bind to cancer cells, induce apoptosis, block cell proliferation
and block angiogenesis.
Selected Articles:
* indicates a RUMBA student participant.
Soto, J. G., Powell, R. L., Reyes, S. R., Wolana, L.,
Swanson, L. J.*, Sanchez, E. E., and Perez, J. C. Genetic
variation of a disintegrin gene found in the American copperhead
snake (Agkistrodon contortrix). (Accepted 11/9, 2005 to
GENE).
Sanchez, E.
E., Galan, J. A., Russell, W. K., Soto, J. G., Rusell, D.
H., and Perez, J.C. (In press) Isolation and
characterization of two disintegrins inhibiting ADP-induced
human platelet aggregation from the venom of Crotalus
scutulatus scutulatus (Mohave rattlesnake). Toxicology
and Applied Pharmacology.
Sanchez, E. E., Galan, J. A., Powell, R., Reyes, S. R., Soto,
J. G., Russell, W. K., Rusell, D. H., and Perez, J.C.
(2005a) Disintegrin, hemorrhagic, and proteolytic activities of
Crotalus scutulatus scutulatus (Mohave rattlesnake)
venoms lacking the Mojave neurotoxin (Mta) gene. Comparative
Biochemistry and Physiology, Part C 141, 124-132.
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