Department of Bioengineering, Rice University, Houston, TX 77005, USA and Instituto Argentino de Matemática “Alberto P. Calderón”, CONICET, Buenos Aires,
C1083ACA, Argentina
*Corresponding author:
Dr. Ariel Fernández
Department of Bioengineering
Rice
University, Houston, TX 77005
USA and Instituto Argentino de Matemática
"Alberto P. Calderón" CONICET, Buenos Aires, C1083ACA, Argentina E-mail:
ariel@uchicago.edu
Received July 19, 2011; Accepted July 19, 2011; Published July 21, 2011
Citation: Fernández A (2011) Pharmaceutical Industry at the Post-Genomic
Junction. J Postgenom Drug Biomark Develop 1:103e. doi:10.4172/2153-
0769.1000103e
The pharmaceutical industry is in disarray, notwithstanding the
enticing promises of the post-genomic era. Drug discovery appears to be
harder and riskier than ever [1]. Projects get unexpectedly terminated
in mid-stage clinical trials, new targets are getting harder to find,
and successful therapeutic agents are often recalled as idiosyncratic
side effects affecting small patient subpopulations are discovered [2].
Exploiting the huge output of post-genomic studies to address such
problems has proven to be far harder than anticipated. More than
ever, the lead in the pharmaceutical industry depends on the ability
to harness innovative research. In this regard, wrapping [2-15], a basic
concept stemming from fundamental bio molecular research, may well
hold potential to broaden the technological base of the industry and
enable a vigorous recovery.
Wrapping is a relatively novel category in structural biology, in
which the 3D-structure of the target protein is examined not by itself
but in relation to the surrounding solvent [2-5]. More specifically,
wrapping describes the extent to which a protein is capable of protecting
its native structure from water attack or better still, from competing
backbone hydration. It has been recently shown that wrapping provides
the basis for a rational translational approach to molecular targeted
therapy since wrapping defects are fairly unique to the protein targets
[6]. These deficiencies are less conserved across proteins of common
ancestry than the fold, which tends to be shared across homologs. Thus,
a “wrapping drug”, that is, a drug that corrects the wrapping defects
of the target upon binding to it, should in principle permit a better
control of specificity [6]. This idea heralded the advent of the so-called
“wrapping technology” with the overarching goal of designing safer
drugs with reduced side effects [7-11].
The wrapping technology stands at the antipodes of current
discovery endeavors based on high-throughput screening and trial-and error
approaches. Before incarnating as a molecular design concept,
wrapping has been explored from a biophysical and evolutionary
perspective. Thus, wrapping becomes particularly insightful as we
try to characterize the protein-water interface. The emerging drug discovery
platform is rooted in fundamental principles that shape our
current understanding of biological water. The wrapping technology is
implemented with the aid of a bioinformatics toolbox that enables us
to explore the bio molecular and evolutionary basis of drug specificity.
While such a transformative concept is in principle capable of
broadening the technological base of the pharmaceutical industry, a
sobering note is in order. Despite the fact that wrapping designs are
physically sound, ultimately, only clinical trials can fully assess their
therapeutic value and safety. In this regard, and from a practical
perspective, current business models in the pharmaceutical R&D may
not be supple enough to accommodate this type of innovation.
Current business models developed around prevalent discovery
paradigms appear to be getting progressively obsolete and are certainly
inadequate to exploit the output of post-genomic forays. More than
ever, the lead in the pharmaceutical industry will depend on alternative
models with the flexibility to incorporate innovative research and
harvest its fruits. On the other hand, the business context required
for the efficient exploitation of fundamental breakthroughs remains
elusive, and perhaps requires a new breed of leadership.
Standing at the cross roads of drug discovery and academic pursuit,
the wrapping concept may well address basic integrative and functional
problems of the pharmaceutical industry. The success of this and other
key translational concepts depends pivotally on the perceived business
imperatives of the industry leadership.
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