32 research outputs found
Joining S100 proteins and migration:for better or for worse, in sickness and in health
The vast diversity of S100 proteins has demonstrated a multitude of biological correlations with cell growth, cell differentiation and cell survival in numerous physiological and pathological conditions in all cells of the body. This review summarises some of the reported regulatory functions of S100 proteins (namely S100A1, S100A2, S100A4, S100A6, S100A7, S100A8/S100A9, S100A10, S100A11, S100A12, S100B and S100P) on cellular migration and invasion, established in both culture and animal model systems and the possible mechanisms that have been proposed to be responsible. These mechanisms involve intracellular events and components of the cytoskeletal organisation (actin/myosin filaments, intermediate filaments and microtubules) as well as extracellular signalling at different cell surface receptors (RAGE and integrins). Finally, we shall attempt to demonstrate how aberrant expression of the S100 proteins may lead to pathological events and human disorders and furthermore provide a rationale to possibly explain why the expression of some of the S100 proteins (mainly S100A4 and S100P) has led to conflicting results on motility, depending on the cells used. © 2013 Springer Basel
Intramolecular Interactions versus Hydration Effects on <i>p</i>âGuanidinoethyl-phenol Structure and p<i>K</i><sub>a</sub> Values
We analyze the structure, hydration, and p<i>K</i><sub>a</sub> values of <i>p</i>-guanidinoethyl-phenol through
a combined experimental and theoretical study. These issues are relevant
to understand the mechanism of action of the tetrameric form, the
antibacterial compound tetra-<i>p</i>-guanidinoethyl-calixÂ[4]Âarene
(Cx1). The investigated system can also be useful to model other pharmaceutical
drugs bearing a guanidine function in the vicinity of an ionizable
group and the effect of arginine on the p<i>K</i><sub>a</sub> of vicinal ionizable residues (in particular tyrosine) in peptides.
The <i>p</i>-guanidinoethyl-phenol monomer (mCx1) has two
ionizable groups. One important particularity of this system is that
it exhibits high molecular flexibility that potentially leads to enhanced
stabilization in folded structures by direct, strong Coulombic interactions
between the ionizable groups. The first p<i>K</i><sub>a</sub> corresponding to ionization of the âOH group has experimentally
been shown to be only slightly different from usual values in substituted
phenols. However, because of short-range Coulombic interactions, the
role of intramolecular interactions and solvation effects on the acidities
of this compound is expected to be important and it has been analyzed
here on the basis of theoretical calculations. We use a discrete-continuum
solvation model together with quantum-mechanical calculations at the
B3LYP level of theory and the extended 6-311+GÂ(2df,2p) basis set.
Both intra- and intermolecular effects are very large (âŒ70
kcal/mol) but exhibit an almost perfect compensation, thus explaining
that the actual p<i>K</i><sub>a</sub> of mCx1 is close to
free phenol. The same compensation of environmental effects applies
to the second p<i>K</i><sub>a</sub> that concerns the guanidinium
group. Such a p<i>K</i><sub>a</sub> could not be determined
experimentally with standard titration techniques and in fact the
theoretical study predicts a value of 14.2, that is, one unit above
the p<i>K</i><sub>a</sub> of the parent ethyl-guanidinium
molecule