Applications of Peptide Array Technologies
Identification of protein-protein interaction sites
Identifying protein-protein interaction sites has shown to be an extremely
valuable tool enabling scientist to design inhibitors, enhancers as well as
providing information on binding regions of proteins.
Identification of protein-protein interaction sites between CD59 AND C8/C9
terminal components.
CD 59 is a membrane glycoprotein that prevents membrane attack of homologous
complement by interacting with terminal components C8 and C9 and preventing
formation of membrane attack complexes. The interaction domains were easily
identified with pep-array technology and used to construct peptides mimicking
CD59 to prevent MAC attach on host cells.
Epitope Mapping
Epitope mapping has shown to be a powerful tool revealing antibody binding
domains on viral proteins. These regions can be used in diagnostics or even
implemented in vaccine for drug development.
Epitope mapping with the SARS virus:
The SARS peptide arrays were probed with patient and control sera and
developed with anti IgA, IgG and IgM Secondary antibodies to identify epitopes
specifically recognized by infected individuals.
Drug development
using peptide array probing
The rationale behind much
of today's drug development is to develop a molecule that specifically interacts
with a target protein. The molecule is designed to compete with or crowd out
other proteins which would otherwise bind to the target, resulting in either
blocking or enhancing functions of these proteins. Similarly, short peptides can
be used as such molecules to intervene with certain protein functions as shown
in the diagram below.
Whether a synthetic peptide can effectively bind to a target is determined by
the sequence of the peptide. Most peptide drugs that are currently under
development are based on the sequence of native proteins. For the example in the
diagram, the sequence of peptide X can be xxGIFLxx as GIFL is the domain in
Protein B that binds to Protein A. However, in most cases, we only know that the
region xxADEKxx on Protein A is important but we either don't know whether there
is another protein binding to this region, or we don't know which protein could
bind to this region. Thus, it is very difficult to predict the sequence of a
synthetic peptide that will be therapeutically effective.
Peptide domain mimotopes
PepMetric uses its proprietary software to design peptides for specific
targeting. Based on many years of protein biochemistry experience, scientists at
PepMetric have been able to incorporate important parameters of protein-protein
interaction into the programs that now can generate peptide sequences that will
most likely bind to the target region of a given protein. The only information
needed for running the program is the amino acid sequence of the target region.
Candidate peptides can be synthesized in array format on membranes or in a
lyophilized form for testing.
PepMetric is now using our new proprietary software that is faster and more
accurate in generating useful sequences of peptides for specific targeting. We
have also developed other computer programs that allow us to do a bioinformatic
analysis on target proteins and to efficiently search entire genomic and
proteomic databases to obtain important information about interacting proteins
Peptide antibody mimetic
Antibodies are a group of proteins generated by our body's immune system.
Antibodies can bind to specific proteins, usually foreign proteins from other
organisms to protect our body from harm by these foreign entities
Immunological therapies are based on this phenomenon. Using protein or protein
fragments, specific antibodies can be generated in animals. Antibodies produced
by the immunized animal can then be used to: a) identify a protein by binding to
it with markers labeled on the antibody for the purpose of diagnosis or clinical
testing; b) concentrate or isolate a protein by using affinity columns coupled
with an antibody that can bind to the protein, for the purpose of making
biological products; or c) bind to the target proteins of pathogens or other
disease proteins, etc as drugs.
Since the functions of antibodies are all mediated by first binding to a
specific region (epitope) of their target proteins, specifically designed
synthetic peptides which share the epitopes or amino acid sequences with the
original antibodies may do the same job. Generation of specific antibodies is a
tedious and time consuming task that often takes months. In contrast, with the
help of proprietary software programs and peptide array probing techniques, it
takes PepMetric much less time and money than competitors to develop and
generate an antibody-mimetic product which may have therapeutic or diagnostic
value.
Diagnostics, identification of Bio-Markers
Bio-Markers
using array technology
Peptide arrays can be
used to diagnose almost every disease providing their bio-markers are available.
Peptides recognizing those markers can be synthesized on a single array and one
test can simultaneously screen for all markers. High throughput and high
resolution make it possible to distinguish the slightest difference between two
disease markers.
In addition, unlike DNA arrays, the detection of disease markers on a peptide
array is technically very straightforward and easy to operate. Therefore, the
peptide array will provide a powerful tool for clinical diagnosis in the future.