β2-Glycoprotein-I based peptide regulate endothelial-cells tissue-factor expression via negative regulation of pGSK3β expression and reduces experimental-antiphospholipid-syndrome.

Antiphospholipid syndrome (APS) is characterized by thromboembolic phenomena and recurrent fetal loss associated with elevated circulating anti-phospholipid/beta2glycoprotein-I(β2GPI)-binding-antibodies(Abs). Individual APS patients harbor diverse clusters of circulating anti-β2GPI Abs, targeting different epitopes on the β2GPI molecule. Our novel approach was to construct a peptide composed of β2GPI-ECs-binding-site (phospholipids-membrane), named "EMBI".

Restrain of bone growth by estrogen-mimetic peptide-1 (EMP-1): a micro-computed tomographic study.

Estrogen has a key role in the regulation of skeletal growth and maintenance of bone mass. Recently, we developed peptides having estrogen-like activity as potential estrogen-based new drugs. The aim of the present study was to evaluate the influence of long-term administration of the most efficacious of these peptides, the hexapeptide EMP-1 (VSWFFE), on bone mass and development.

Design, synthesis, and evaluation of peptides with estrogen-like activity.

Currently used antiestrogenic drugs against hormone-dependent breast cancer, and estrogenic drugs used in treatment of osteoporosis, are associated with risk factors. Therefore, there is a strong need to develop selective estrogen receptor modulators with better tissue selectivity. In a recent study (Peptides, 2002, Vol.

On proteins, grids, correlations, and docking.

The activity of a living cell can be portrayed as a network of interactions involving proteins and nucleic acids that transfer biological information. Intervention in cellular processes requires thorough understanding of the interactions between the molecules, which can be provided by docking techniques. Docking methods attempt to predict the structures of complexes given the structures of the component molecules.

The binding site of acetylcholine receptor: from synthetic peptides to solution and crystal structure.

Our group has been employing short synthetic peptides, encompassing sequences from the acetylcholine receptor (AChR) alpha-subunit for the analysis of the binding site of the AChR. A 13-mer peptide mimotope, with similar structural motifs to the AChR binding region, was selected by alpha-bungarotoxin (alpha-BTX) from a phage-display peptide library. The solution structure of a complex between this library-lead peptide and alpha-BTX was solved by NMR spectroscopy.

Design and synthesis of peptides that bind alpha-bungarotoxin with high affinity and mimic the three-dimensional structure of the binding-site of acetylcholine receptor.

Alpha-bungarotoxin (alpha-BTX) is a highly toxic snake neurotoxin that binds to acetylcholine receptor (AChR) at the neuromuscular junction, and is a potent inhibitor of this receptor. In the following we review multi-phase research of the design, synthesis and structure analysis of peptides that bind alpha-BTX and inhibit its binding to AChR. Structure-based design concomitant with biological information of the alpha-BTX/AChR system yielded 13-mer peptides that bind to alpha-BTX with high affinity and are potent inhibitors of alpha-BTX binding to AChR (IC(50) of 2 nM).

Electrostatics in protein-protein docking.

A novel geometric-electrostatic docking algorithm is presented, which tests and quantifies the electrostatic complementarity of the molecular surfaces together with the shape complementarity. We represent each molecule to be docked as a grid of complex numbers, storing information regarding the shape of the molecule in the real part and information regarding the electrostatic character of the molecule in the imaginary part. The electrostatic descriptors are derived from the electrostatic potential of the molecule.

A synthetic peptide with estrogen-like activity derived from a phage-display peptide library.

We describe a novel approach to develop peptides with estrogen like activity using a monoclonal antibody specific to estradiol (mAb E2-15) for the affinity selection of phage displayed peptides from a combinatorial peptide library. Based on the sequences of the selected phage, we synthesized a 15-mer linear peptide LPALDPTKRWFFETK which was derivatized to a 23 mer cyclic peptide CAELPALDPTKRWFFETKPPPPC. Both peptides displayed estrogen-like activity according to the following criteria:(i) in inhibiting the binding of [3H]estradiol to mAb E2-15 and to estrogen receptor (ER)alpha; (ii) in inducing transcriptional activity in MCF7 human breast cancer cells transfected with an estrogen receptor element luciferase construct and (iii) in causing an increase in creatine kinase specific activity in rat tissues in vivo.