Opioid peptides: synthesis and biological properties of [(N gamma-glucosyl,N gamma-methoxy)-alpha, gamma-diamino-(S)-butanoyl]4-deltorphin-1-neoglycopeptide and related analogues

The [D-Ala2]deltorphin 1 sequence in which the aspartic acid residue is replaced by the N gamma-OCH3-alpha, gamma-diamino (S) butanoyl residue was synthesized using the Fmoc-chemistry-based solid phase procedure. The resulting deltorphin analogue was chemoselectively glucosylated by reaction with unprotected D-glucose (Glc). The Asn4-, (2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-beta-D-galactopyranosyl)-Asn4- and the (2-acetamido-2-deoxy-D-galactopyranosyl)-Asn4-deltorphin I were also prepared for comparison. The affinity of the new compounds for the delta-opioid receptor was expressed by the inhibition constant (Ki) of the binding of the delta-receptor selective ligand [3H]naltrindole (NTI) to rat brain membrane preparations. The in vitro biological activity of the synthetic peptides was compared with that of the mu-opioid receptor agonist dermorphin in guinea pig ileum (GPI) preparations and with that of the delta-opioid receptor agonist deltorphin I in mouse vas deferens (MVD) preparations. The substitution of Asp4 with Asn failed to affect drastically the Ki and IC50 values for delta-sites, suggesting that an electrostatic interaction does not play an essential role in the binding to delta-opioid sites. The steric hindrance of the side chain of the residue in position 4 affects binding to delta-sites. The increase of the Ki value is smaller when the sugar-peptide linkage involves the gamma-nitrogen of the Dab residue in comparison with the Asn amide side chain.     

Demystifying the three dimensional structure of G protein-coupled receptors (GPCRs) with the aid of molecular modeling

We review our recent work on adenosine receptors, a family of GPCRs; focusing our attention on A3 adenosine receptor, we have demonstrated that the reciprocal integration of different theoretical and experimental disciplines can be very useful for the successful protein-based design of new, potent and selective receptor ligands.     

Numerical Approximation of Time Domain Electromagnetic Scattering from a Thin Wire

We present two new stable schemes for computing the current induced on the surface of a thin wire by an incident time-dependent electromagnetic field. The problem involves solving a retarded potential integral equation (RPIE). One algorithm solves the previously studied reduced kernel RPIE problem, and the other solves the more complicated exact kernel RPIE problem (for which there are no previous numerical results). Both algorithms behave stably for arbitrarily chosen values of the mesh size. Test experiments and numerically computed values of the induced current are presented.     

Teilautomatisches Bestimmungsverfahren für Adrenalin und Noradrenalin im Harn

The method of Weil-Malherbe and Bigelow [21,22] for the fluorometric determination of urinary epinephrine and norepinephrine was adapted to the AutoAnalyzer. The criteria of reliability of the method were determined. The normal range for the excretion or epinephrine and norepinephrine in the 24 h-urine is given for a sample of 47 women and 51 men.