Biomedical Engineering Reference
In-Depth Information
therapeutics, (c) complex kinetic analyses and mathematical simulations/modeling
describing binding modes, off-target interactions and even binding dynamics, and (d)
preparation of structural models by homology to known membrane protein structures,
an increasingly important approach as more crystal structures of membrane proteins
or their fragments are solved. Computational approaches facilitated by the PMDC
require “real” structural data in order to be reliable. Component (ii) of the PMDC
enables the preparation of membrane proteins to be used for X-ray, NMR and cryo-
electron microscopic structure determination. In addition, it is also advantageous to
construct a relational database for membrane protein properties and experimental
data. This provides the basis of intensive data mining and meta-analyses of data
developed by several research groups, and makes the results of research much more
readily available to the larger community of researchers working in the field.
Target Investigation Core (TIC) The potential of membrane proteins as therapeu-
tic targets has been realized only for GPCR so far. An enormous range of mem-
brane proteins implicated in disease processes remains to be exploited. The TIC pro-
vides automated fluorescence-based and electrophysiological equipment to quickly
acquire information on the behavior of multiple membrane protein variants, and to
rapidly screen membrane proteins for inter-molecular (protein-protein, or protein-
drug) interactions. Possible drug-like lead compounds can be identified by the TIC.
7.1 Lipids as Markers in Anti-Cancer Treatment: Lipid
Membrane Binding of Aptamers
The induction of programmed cell death (apoptosis) is both a desired outcome of
cancer therapy and a potential target allowing imaging and modulation of therapeu-
tic effects. A novel information-driven approach has been recently discovered [ 47 ]
which can be generalized for the development of theranostic (therapeutic and diag-
nostic) drugs targeting cellular changes related to apoptotic transformation. Apop-
tosis is a vital, highly regulated, natural process that contributes to the development
and maintenance of human and animal cells [ 21 , 50 ]. Apoptosis plays multiple roles
in the normal development of organisms, extending from embryonic development
to the maintenance of normal cell homeostasis [ 13 , 34 , 35 ]. Malfunctioning of the
apoptotic process leads to the proliferation of many types of cancer, due to inade-
quate control of cell homeostasis. It is recognized that evasion of apoptosis is one
of the hallmarks of cancer development and progression [ 17 ]. There are a number
of related cellular processes observed during apoptosis including phosphatidylserine
(PS) externalization, caspase activation, chromatin and nucleus condensation, reduc-
tion in cytoplasm volume and DNA degradation [ 13 ]. Drugs targeting and modulating
apoptosis have a recognized potential in cancer diagnosis and therapy.
There are two main apoptotic pathways: the death receptor (extrinsic) pathway
and the mitochondrial (intrinsic) pathway [ 39 ]. The death receptor pathway (MAPK)
is activated by the binding of FAS or TRAIL ligands to their receptors (DR4/5),
stimulating receptor aggregation. In the mitochondrial pathway, pro-survival sig-
 
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