From morphine to endogenous opioid peptides, e.g., endorphins: the endless quest for the perfect painkiller

Opium was known since the Neolithic era and in 5th century wild Papaver use was reported to induce sleep and relieving pain. First active component isolated from Opium was morphine, the paradigm of a natural product discovered 150 years before isolation of endogenous opioid ligands, brain pentapeptide enkephalins. Since then many endorphin peptides and their mode of action were discovered. Native endorphins were characterized thanks to the synthetic antagonist naloxone

Peptides and Peptidomimetics as Inhibitors of Enzymes Involved in Fibrillar Collagen Degradation

Collagen fibres degradation is a complex process involving a variety of enzymes. Fibrillar collagens, namely type I, II, and III, are the most widely spread collagens in human body, e.g., they are responsible for tissue fibrillar structure and skin elasticity. Nevertheless, the hyperactivity of fibrotic process and collagen accumulation results with joints, bone, heart, lungs, kidneys or liver fibroses. Per contra, dysfunctional collagen turnover and its increased degradation leads to wound healing disruption, skin photoaging, and loss of firmness and elasticity. In this review we described the main enzymes participating in collagen degradation pathway, paying particular attention to enzymes degrading fibrillar collagen. Therefore, collagenases (MMP-1, -8, and -13), elastases, and cathepsins, together with their peptide and peptidomimetic inhibitors, are reviewed. This information, related to the design and synthesis of new inhibitors based on peptide structure, can be relevant for future research in the fields of chemistry, biology, medicine, and cosmeceuticals

Label-free method for anti-glucopeptide antibody detection in Multiple Sclerosis

Surface plasmon resonance technique is particularly interesting in immunology because it has the potential to visualize label-free antigen-antibody interactions in real-time, thus enabling antibody detection and monitoring. Herein we release the guidelines for the correct use of a method to detect specific antibodies directly in Multiple Sclerosis patients’ sera using a glucopeptide-based label-free biosensor. The protocol describes the strategy employed for the immobilization of glucopeptide antigen onto a gold sensor chip and the evaluation of the specific binding of serum antibodies to the immobilized antigen. • Label-free method for the real time screening of disease-specific antibodies within a few minutes; • The described protocol employs small quantities of glucopeptide antigen and blood serum samples saving method-cost; • Stability of the immobilized glucopeptide antigen guarantees the regeneration of the surface allowing re-use the immunosensor with high automated throughput. The antibodies detected using the described methodology can be evaluated as biomarkers of Multiple Sclerosis. The SPR detection system is able to characterize antibodies significantly different from those evaluated in the classical enzyme-linked immunosorbent assays (ELISA)

A Photochromic Azobenzene Peptidomimetic of a β-Turn Model Peptide Structure as a Conformational Switch

The insertion of azobenzene moiety in complex molecular protein or peptide systems can lead to molecular switches to be used to determine kinetics of folding/unfolding properties of secondary structures, such as α-helix, β-turn, or β-hairpin. In fact, in azobenzene, absorption of light induces a reversible trans ↔ cis isomerization, which in turns generates a strain or a structure relaxation in the chain that causes peptide folding/unfolding. In particular azobenzene may permit reversible conformational control of hairpin formation. In the present work a synthetic photochromic azobenzene amino acid derivative was incorporated as a turn element to modify the synthetic peptide [Pro7,Asn8,Thr10]CSF114 previously designed to fold as a type I β-turn structure in biomimetic HFA/water solution. In particular, the P-N-H fragment at positions 7–9, involved in a β-hairpin, was replaced by an azobenzene amino acid derivative (synthesized ad hoc) to investigate if the electronic properties of the novel peptidomimetic analog could induce variations in the isomerization process. The absorption spectra of the azopeptidomimetic analog of the type I β-turn structure and of the azobenzene amino acid as control were measured as a function of the irradiation time exciting into the respective first ππ* and nπ* transition bands. Isomerization of the azopeptidomimetic results strongly favored by exciting into the ππ* transition. Moreover, conformational changes induced by the cis↔ trans azopeptidomimetic switch were investigated by NMR in different solvents

DOTA-Derivatives of Octreotide Dicarba-Analogs with High Affinity for Somatostatin sst2,5 Receptors

In vivo somatostatin receptor scintigraphy is a valuable method for the visualization of human endocrine tumors and their metastases. In fact, peptide ligands of somatostatin receptors (sst's) conjugated with chelating agents are in clinical use. We have recently developed octreotide dicarba-analogs, which show interesting binding profiles at sst's. In this context, it was mandatory to explore the possibility that our analogs could maintain their activity also upon conjugation with DOTA. In this paper, we report and discuss the synthesis, binding affinity and conformational preferences of three DOTA-conjugated dicarba-analogs of octreotide. Interestingly, two conjugated analogs exhibited nanomolar affinities on sst(2) and sst(5) somatostatin receptor subtypes

Ring-Opening Polymerisation of rac-Lactide Using a Calix[4]arene-Based Titanium (IV) Complex

cone-25,27-Dipropyloxy-26,28-dioxo-calix[4]arene titanium (IV) dichloride(1)has been assessed in the ring-opening polymerisation ofrac-lactide (L,D-LA). The polymers formed (PLDA) turned out to display an isotactic stereoblock microstructure (determined by NMR) despite the fact that the catalyst hasC2vsymmetry. Two techniques were applied for initiating the polymerisation reaction, microwave irradiation, and conventional thermal treatment. The polymers obtained were all characterised by NMR, IR, HPLC-SEC, DSC, and MALDI-TOF analysis. The use of microwave irradiation, applied for the first time to calixarene-based catalysts in the presence of therac-lactide monomer, increased the polymerisation rate compared with that obtained by the other method. On the other hand, standard thermal treatment enabled a slightly better control than microwave irradiation over the molecular weight and molecular weight distribution of the polylactides formed