A. F. Santos

Antitumor Effect of a Novel Proapoptotic Peptide that Impairs the Phosphorylation by the Protein Kinase 2 (Casein Kinase 2)

Protein Kinase (casein kinase 2, CK2) is a serine-threonine kinase that is frequently dysregulated in many human tumors. Therefore we hypothesized that peptides capable of binding to the CK2 acidic domain may exhibit potential anticancer properties. By screening a random cyclic peptide phage display library, we have identified a novel peptide, P15, that abrogated CK2 phosphorylation by blocking the substrate in vitro. To verify its potential antineoplastic effect, P15 was fused to the cell-penetrating peptide derived from the HIV-Tat protein. Interestingly, P15-Tat induced apoptosis as evidenced by rapid caspase activation and cellular cytotoxicity in a variety of tumor cell lines. Furthermore, direct injection of P15-Tat into C57BL6 mice bearing day 7-established solid tumors, resulted in substantial regression of the tumor mass. Our findings describe a new proapoptotic cyclic peptide that blocks the CK2 phosphorylation and exhibits antitumor effect in vivo, indicating that the P15 peptide may potentially be used clinically to treat solid tumors or as an adjuvant for cancer therapy.

Expression and folding of an interleukin-2-proinsulin fusion protein and its conversion into insulin by a single step enzymatic removal of the C-peptide and the N-terminal fused sequence

We report the expression in E. coli of a proinsulin fusion protein carrying a modified interleukin‐2 N‐terminal peptide linked to the N‐terminus of proinsulin by a lysine residue. The key aspects investigated were: (a) the expression of the fused IL2‐PI gene, (b) the folding efficiency of the insulin precursor when still carrying the N‐fused peptide and (c) the selectivity of the enzymatic cleavage reaction with trypsin in order to remove simultaneously the C‐peptide and the N‐terminal extension. It was found that this construction expresses the chimeric proinsulin at high level (20%) as inclusion bodies; the fused protein was refolded at 100–200 μg/ml to yield about 80% of correctly folded proinsulin and then it was converted into insulin by prolonged reaction (5 h) with trypsin and carboxypeptidase B at a low enzyme/substrate rate (1:600). This approach is based on a single enzymatic reaction for the removal of both the N‐terminal fused peptide and the C‐peptide and avoids the use of toxic cyanogen bromide.

Horava-Lifshitz gravity and Godel Universe

We prove the consistency of the G{o}del metric with the Horava-Lifshitz gravity whose action involves terms with z=1, z=2 and z=3. We show that, for different relations between the parameters of the theory, this consistency is achieved for different classes of matter, in particular, for the small cosmological constant it is achieved only for the exotic matter, that is, ghosts or phantom matter.

Gödel solution in the bumblebee gravity

Here, we consider a gravity theory involving a spontaneous Lorentz symmetry breaking called the bumblebee model. We show that, at certain values of the bumblebee field, the Godel metric is consistent within this theory.

Dynamical Chern–Simons modified gravity, Gödel Universe and variable cosmological constant

Abstract We study the condition for the consistency of the Godel metric with the dynamical Chern–Simons modified gravity. It turns out to be that this compatibility can be achieved only if the cosmological constant is variable in the space.

Free energy of Lorentz-violating QED at high temperature

In this paper we study the one- and two-loop contribution to the free energy in QED with Lorentz symmetry breaking introduced via constant CPT-even Lorentz-breaking parameters at the high temperature limit. We find the impact of the Lorentz-violating term for the free energy and carry out a numerical estimation for the Lorentz-breaking parameter.

THE GÖDEL METRIC IN THE CHERN-SIMONS MODIFIED GRAVITY

We discuss the consistency of the Godel metric within the Chern-Simons modified gravity, both for external and dynamical Chern-Simons coefficients.

Gödel-type solutions within the f(R,Q) gravity

In this paper, we deal with the

Identification of nuclear proteins of small cell lung cancer cell line H82: An improved procedure for the analysis of silver‐stained proteins

f(R,Q)

Dynamical Chern-Simons modified gravity and Friedmann-Robertson-Walker metric

gravity whose action depends, besides of the scalar curvature