Structural Analysis of alpha-Fetoprotein (AFP)-like Peptides with Anti-Breast-Cancer Properties

The abundance of alpha-fetoprotein (AFP), a natural protein produced by the fetal yolk sac during pregnancy, correlates with lower incidence of estrogen receptor positive (ER+) breast cancer. The pharmacophore region of AFP has been narrowed down to a four amino acid (AA) region in the third domain of the 591 AA peptide. Our computational study focuses on a 4-mer segment consisting of the amino acids threonine-proline-valine-asparagine (TPVN). We have run replica exchange molecular dynamics (REMD) simulations and used 120 configurational snapshots from the total trajectory as starting configurations for quantum chemical calculations. We optimized structures using semiempirical (PM3, PM6, PM6-D2, PM6-H2, PM6-DH+, PM6-DH2) and density functional methods (TPSS, PBE0, M06-2X). By comparing the accuracy of these methods against RI-MP2 benchmarks, we devised a protocol for calculating the lowest energy conformers of these peptides accurately and efficiently. This protocol screens out high-energy conformers using lower levels of theory and outlines a general method for predicting small peptide structures.

Experimental pneumococcal meningitis causes central nervous system pathology without inducing the 72-kd heat shock protein

We examined whether experimental pneumococcal meningitis induced the 72-kd heat shock protein (HSP72), a sensitive marker of neuronal stress in other models of central nervous system (CNS) injury. Brain injury was characterized by vasculitis, cerebritis, and abscess formation in the cortex of infected animals. The extent of these changes correlated with the size of the inoculum (P less than 0.003) and with pathophysiologic parameters of disease severity, i.e., cerebrospinal fluid (CSF) lactate (r = 0.61, P less than 0.0001) and CSF glucose concentrations (r = -0.55, P less than 0.0001). Despite the presence of numerous cortical regions having morphologic evidence of injury, HSP72 was not detected in most animals. When present, only rare neurons were HSP72 positive. Western blot analysis of brain samples confirmed the paucity of HSP72 induction. The lack of neuronal HSP72 expression in this model suggests that at least some of the events leading to neuronal injury in meningitis are unique, when compared with CNS diseases associated with HSP72 induction.

NIKH: 1914

This digital object was funded in part through a grant from the Andrew Mellon Foundation. The digitalization of this object was part of a collaborative effort with the Washington Research Library Consortium and George Washington University.

The Bison: 2011: Part 1

This digital object was funded in part through a grant from the Andrew W. Mellon Foundation. The digitalization of this object was part of a collaborative effort with the Washington Research Library Consortium and George Washington University.

The Bison: 2011: Part 2

This digital object was funded in part through a grant from the Andrew W. Mellon Foundation. The digitalization of this object was part of a collaborative effort with the Washington Research Library Consortium and George Washington University.

The Bison: 2011: Part 3

This digital object was funded in part through a grant from the Andrew W. Mellon Foundation. The digitalization of this object was part of a collaborative effort with the Washington Research Library Consortium and George Washington University.

The Bison: 2011: Part 4

This digital object was funded in part through a grant from the Andrew W. Mellon Foundation. The digitalization of this object was part of a collaborative effort with the Washington Research Library Consortium and George Washington University.

The Bison: 2009

This digital object was funded in part through a grant from the Andrew W. Mellon Foundation. The digitalization of this object was part of a collaborative effort with the Washington Research Library Consortium and George Washington University.

The Bison: 2010

This digital object was funded in part through a grant from the Andrew W. Mellon Foundation. The digitalization of this object was part of a collaborative effort with the Washington Research Library Consortium and George Washington University.