Signal transduction pathways triggered by selective formylpeptide analogues in human neutrophils.

Human neutrophils are highly specialised for their primary function, i.e. phagocytosis and destruction of microorganisms.

Chemotactic peptides: fMLF-OMe analogues incorporating proline-methionine chimeras as N-terminal residue.

The new fMLF analogues 1-4, incorporating chimeric S-proline-methionine residues (namely the homochiral cis-4(S)-methylthio-(S)-proline (10) and the heterochiral trans-4(R)-methylthio-(S)-proline) (17) in place of the native S-methionine, have been prepared; their solution conformation and activity as agonists or antagonists of formylpeptide receptors have been studied. In addition to peptides 1-4, which maintain the Met gamma-thiomethyl-ether function, the analogues Boc-PLF-OMe (18) and For-PLF-OMe (19) devoid, as compared with 1-4, of position 1 side chain, have been synthesized and their activity examined.

Synthesis and biological activity of the first cyclic biphalin analogues.

Biphalin is a linear octapeptide with strong opioid activity. Its structure is based on two identical sequences derived from enkephalins joined C-terminal to C-terminal by an hydrazide bridge (Tyr-D-Ala-Gly-Phe-NH-NH<--Phe<--Gly<--D-Ala<--Tyr). In this study we present the design, synthesis, and biological evaluation of the first cyclic biphalin analogues.

Carboplatin sustained delivery system using injectable microspheres.

A controlled carboplatin delivery system using biodegradable polymer has been used in this study. The purpose was to evaluate the local and systemic effects of injectable, biodegradable microspheres containing carboplatin when injected as aqueous suspension subcutaneously in rats. Biocompatibility and toxicity of empty microspheres and microspheres loaded with carboplatin were evaluated by clinical and histological examination.

Synthesis and biological evaluation of new biphalin analogues with non-hydrazine linkers.

Biphalin is a potent opioid peptide agonist, with a palandromic structure, composed of two enkephalin-like active fragments connected tail to tail by a hydrazine linker (Tyr-D-Ala-Gly-Phe-NH-NH<-Phe<-Gly<-D-Ala<-Tyr). This study presents the synthesis and in vitro bioassays of six new biphalin analogues with three different non-hydrazine linkers, some of which have higher binding affinity and bioactivity than biphalin.

Peptides containing 4-amino-1,2-dithiolane-4-carboxylic acid (Adt): conformation of Boc-Adt-Adt-NHMe and NH...S interactions.

To study the conformational preferences induced by the insertion of the 4-amino-1,2-dithiolane-4-carboxylic acid (Adt) residue into a peptide backbone, the achiral N-protected dipeptide methylamide Boc-Adt-Adt-NHMe (1) was synthesized and its crystal state and solution conformation studied and compared with that exhibited by its carba-analogue Boc-Ac5c-Ac5c-NHMe containing two residues of 1-aminocyclopentane-1-carboxylic acid (Ac5c). Compound 1 in the crystal adopts a type-III beta-turn conformation and an analogous structure is that preferred in chloroform solution as established by 1H-NMR and NOE information. In the crystal packing three different Adt rings form a cavity and the involved sulphur atoms give rise to unusual multiple interactions with one NH group.

Peptide backbone folding induced by the C(alpha)-tetrasubstituted cyclic alpha-amino acids 4-amino-1,2-dithiolane-4-carboxylic acid (Adt) and 1-aminocyclopentane-1-carboxylic acid (Ac5c). A joint computational and experimental study.

The conformational study of a new group of synthetic peptides containing 4-amino-1,2-dithiolane-4-carboxylic acid (Adt), a cysteine-related achiral residue, has been carried out through a joint application of computational and experimental methodologies. Molecular Dynamics simulations clearly suggest the tendency of this molecule to adopt a gamma-turn conformation in vacuum and help in analyzing the complex and crucial conformational behaviour of the dithiolane ring which appears to preferentially adopt a C(S)-like structure. Electronic structure calculations carried out in solution using the Density Functional Theory also indicate the preservation of the gamma-like folding in apolar solvents and the helix-like one in more polar solvents.

On-line biofilm monitoring by "BIOX" electrochemical probe.

The innovative electrochemical monitoring probe (BIOX) recently developed to improve the antifouling treatments of cooling systems in industrial plants is presented. On the basis of the good results obtained from applications on marine sites, some research has been stated to validate this technique in biofilm growth and prevention of microbial corrosion in fresh and drinking waters.

Proline-glutamate chimeras in isopeptides. Synthesis and biological evaluation of conformationally restricted glutathione analogues.

The two novel diastereoisomeric glutathione analogues 1 and 2 have been designed and synthesized by replacing the native gamma-glutamylic moiety with the conformational rigid skeleton of cis- or trans-4-carboxy-L-proline residue. Both analogues have been obtained by following the solution phase peptide chemistry methodologies and final reduction of the corresponding disulfide forms 13 and 14. The two analogues 1 and 2 have been tested towards gamma-glutamyltranspeptidase (gamma-GT) and human glutathione S-transferase (hGST P1-1).

Isopeptide bonds in chemotactic tripeptides. Synthesis and activity of lysine-containing fMLF analogs.

In order to explore the properties of chemotactic N-formylpeptides containing isopeptide bonds within their backbones, a group of lysine-containing analogs of the prototypical chemotactic tripeptide N-formylmethionyl-leucyl-phenylalanine (fMLF) was synthesized. The new analogs were designed by adding to the HCO-Met or Boc-Met residue a dipeptide fragment made up of Lys and Phe residues joined through Lys N alpha or N epsilon bonds, in all possible combinations. Thus, the following six pairs of tripeptides were synthesized and examined for their bioactivity: RCO-Met-Lys(Z)-Phe-OMe (2a, b), RCO-Met-Lys(Z-Phe)-OMe (3a, b), Z-Lys(RCO-Met)-Phe-OMe (4a, b), Z-Phe-Lys(RCO-Met)-OMe (5a, b), RCO-Met-Phe-Lys(Z)-OMe (6a, b) and Z-Lys(RCO-Met-Phe)-OMe (7a, b), with R=OC(CH3)(3 )and R=H for compounds a and b, respectively.

Gorham's disease: a literature review and case reports.

Gorham's disease (disappearing bone disease, massive osteolysis, idiopathic osteolysis, essential osteolysis, progressive atrophy of bone, spontaneous absorption of bone, phantom bone, hemangiomatosis/lymphangiomatosis of bone, progressive osteolysis) is an extremely rare occurrence. There are fewer than 150 reported cases in the literature. This disorder can be characterized by spontaneous or posttraumatic progressive resorption of bone.

A statistical analysis on the reliability of the proximal articular set angle.

The authors investigated the statistical relationship and significance between the transverse and sagittal plane proximal articular set angles both radiographically and intraoperatively. The analysis revealed a highly significant difference between the means of the respective measurements. Although the radiographic and intraoperative findings were found to be related for the transverse plane proximal articular set angle, the transverse plane PASA was approximately 7 degrees greater when measured intraoperatively.