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P Temussi

Publications and source records attributed to P Temussi.

6 recordsLinked to original sources
PubMed1999

Solution structure of human beta-endorphin in helicogenic solvents: an NMR study.

Beta-endorphin is the largest natural opioid peptide. The knowledge of its bioactive conformation might be very important for the indirect mapping of the active site of opioid receptors. We have studied beta-endorphin in a variety of solution conditions with the goal of testing the intrinsic tendency of its sequence to assume a regular fold. We ran NMR experiments in water, dimethylsulfoxide and aqueous mixtures of methanol, ethylene glycol, trifluoroethanol, hexafluoracetone trihydrate and dimethylsulfoxide. The solvent in which the peptide is more ordered is the hexafluoracetone trihydrate/water mixture. The helical structure detected for beta-endorphin in this mixture at 300 K extends for the greater part of its address domain, hinting at a possible mechanism of interaction with opioid receptors: a two-point attachment involving an interaction of the helical part of the address domain (PLVTLFKNAIIKNAY) with one of the transmembrane helices and a classical interaction of the message domain (YGGF) with the receptor subsite common to all opioid receptors.

Amino Acid Sequence↗
PubMed1999

Tendamistat surface accessibility to the TEMPOL paramagnetic probe.

TEMPOL, the soluble spin-label 4-hydroxy-2,2,6,6-tetramethyl-piperidine-1-oxyl, has been used to determine the surface characteristics of tendamistat, a small protein with a well-characterised structure both in solution and in the crystal. A good correlation has been found between predicted regions of exposed protein surface and the intensity attenuations induced by the probe on 2D NMR TOCSY cross peaks of tendamistat in the paramagnetic water solution. All the high paramagnetic effects have been interpreted in terms of more efficient competition of TEMPOL with water molecules at some surface positions. The active site of tendamistat coincides with the largest surface patch accessible to the probe. A strong hydration of protein N and C termini can also be suggested by this structural approach, as these locations exhibit reduced paramagnetic perturbations. Provided that the solution structure is known, the use of this paramagnetic probe seems to be well suited to delineate the dynamic behaviour of the protein surface and, more generally, to gain relevant information about the molecular presentation processes.

Binding Sites↗
PubMed1996

Dmt-Tic-OH a highly selective and potent delta-opioid dipeptide receptor antagonist after systemic administration in the mouse.

Dmt-Tic-OH (DTOH) and Dmt-Tic-Ala-OH (DTAOH), effective antagonists in vitro, represent a new potent opioid dipeptides for the delta-opioid receptor (Ki delta of 0.022 nM and a selectivity, Ki mu/Ki delta, of 150,000 for DTOH; Ki delta of 0.285 nM and a selectivity Ki mu/Ki delta, of 20,4 for DTAOH). In the present study we considered the pharmacological activity of these two new delta opioid peptide receptor antagonists in vivo. Therefore, we have evaluated their possible antagonistic activity against the antinociception induced by the highly selective delta opioid receptor agonist, [D-Ala2]deltorphin II (DEL). Furthermore, these two delta opioid peptide receptor antagonists were injected centrally or peripherally in order to assess their ability to act also after systemic administration. Concurrent i.c.v. injection of DTOH or DTAOH (0.5-1.0-2.0 nM) with DEL (5 nmol) induced a significant reduction of DEL antinociception. By contrast, while DTOH (10-20-40 mg/kg) administered peripherally (i.p., s.c. or i.v.) was also able to reduce DEL antinociception, DTAOH failed. The present results indicate that DTOH is the first opioid dipeptide with delta antagonist activity after systemic administration and it could be important in the clinical and therapeutic applications.

Animals↗
PubMed1989

Ala analogues of the cyclolinopeptide A.

Analogues of cyclolinopeptide A, due to the replacement of each amino acid in the Pro1-Pro2-Phe3-Phe4 sequences with an L-Ala residue, were synthesized by classical method in solution. Mixed anhydride and N,N'-dicyclohexylcarbodiimide coupling methods have been used for the synthesis of both linear and cyclic peptides. The products were characterized by Rf values and uv spectra, as well as by fast atom bombardment spectroscopy. 1H-nmr studies on [Ala2] analogues are also reported. Preliminary data in CDCl3 solution, at low temperature, seems more promising.

Alanine↗