Biomedical subjects

Rafal Kruszynski

Publications and source records attributed to Rafal Kruszynski.

8 recordsLinked to original sources

PubMed2006

Bond-valence parameters of lanthanides.

Ln-O and Ln-N bond-valence parameters have been computed in coordination complexes for lanthanides (Ln) at oxidation states other than +3 (Ce(IV), Sm(II), Eu(II) and Yb(II)). Moreover, Ln-Cl, Ln-S and Ln-C(pi-bonded) bond-valence parameters are presented, as calculated for coordination compounds. In general, the bond-valence parameters decrease in the order Ln-O > Ln-C > Ln-N > Ln-Cl > Ln-S. It has been found that the values of bond-valence parameters decrease with increasing lanthanide atomic number for coordination compounds. As expected, the values of lanthanide-oxygen and lanthanide-nitrogen bond-valence parameters diminish with increasing lanthanide oxidation state. Several examples are given where the total valence of the lanthanide ion is apparently incorrectly assigned, as well as cases where bond-valence method calculations confirm the doubtful oxidation state assignment.

Journal Article↗

PubMed2005

Synthesis and antinociceptive activity of cyclic endomorphin-2 and morphiceptin analogs.

Cyclic analogs of the opioid peptides endomorphin-2 and morphiceptin of the type Tyr-X-Phe-Phe-Y-NH2 and Tyr-X-Phe-D-Pro-Y-NH2 (X = Lys or Asp and Y = Lys or Asp), respectively, were synthesized in order to test their structure-activity relationships. Antinociceptive activity of the new analogs was assessed in the hot-plate test after intracerebroventricular administration in mice. The strong analgesic effect was observed for the analogs with Asp in position 2, while the analogs with Lys in the second position were inactive. Antinociception caused by Asp2 analogs was dose-dependent and reversed by the concomitant administration of the universal opioid antagonist naloxone and by the selective kappa antagonist, nor-BNI. However, receptor binding studies revealed poor affinity of all cyclic analogs at the mu-opioid receptor and no affinity at delta- and kappa-opioid receptors. It is most likely that the new cyclic analogs produced their antinociception by the release of dynorphin A, which subsequently acted on the kappa-opioid receptor.

Analgesics, Opioid↗

PubMed2005

Synthesis and biological activity of N-methylated analogs of endomorphin-2.

In this paper, we describe the synthesis of a series of endomorphin-2 analogs containing N-methylated amino acids, consecutively in each position. The mu-opioid receptor binding affinities of the new analogs were determined in the displacement experiments. Their in vivo antinociceptive activity was assessed in the hot-plate test in mice after central (icv) and peripheral (ip) administration. [Sar2]endomorphin-2, which had the highest mu-receptor affinity, also showed the strongest analgesic effect when administered centrally and was the only analog that retained activity after peripheral injection.

Animals↗

PubMed2005

Bis{mu-2-[(2,3-dichlorophenyl)amino]benzoato-kappaO}di-mu2-ethoxo-octamethyldi-mu3-oxo-tetratin(IV).

The title compound, [Sn4(CH3)8(C13H8Cl2NO2)2(C2H5O)2O2], is a centrosymmetric dimer, with three linearly fused four-membered Sn-O-Sn-O rings. The coordination polyhedron of the Sn atom bonded to the carboxylate can be described as trigonal-bipyramidal distorted toward square-pyramidal. That of the second Sn atom is similar, but the distortion towards square-pyramidal geometry is greater. The Sn-O and Sn-C distances are 2.020 (2)-2.226 (2) and 2.096 (4)-2.114 (4) A, respectively. The benzene rings of the 2-[(2,3-dichlorophenyl)amino]benzoate ligand subtend an angle of 50.49 (17) degrees; the conformation of the ligand is stabilized by intramolecular N-H...Cl and N-H...O hydrogen bonds. The structure is assembled via pi-pi stacking interactions to form chains parallel to [120].

Anti-Inflammatory Agents↗

PubMed2005

Enzymatic degradation studies of endomorphin-2 and its analogs containing N-methylated amino acids.

In this paper, we describe the synthesis of novel endomorphin-2 analogs, containing N-methylated amino acids, consecutively in each position. The receptor-binding profile of the new analogs and their stability against enzymatic cleavage by commercially available peptidases, carboxypeptidase Y and aminopeptidase M, and a rat brain homogenate are reported. The best analog of this series, [Sar2]endomorphin-2, was almost equipotent with the parent peptide in the mu-receptor-binding assay and was also highly resistant to enzymatic degradation. This analog may be a suitable candidate for the in vivo antinociceptive studies.

Alkylation↗

PubMed2005

New lanthanide-nitrogen bond-valence parameters.

The bond-valence parameters (R(ij)), which connect bond valences and bond lengths, have been computed for lanthanide-nitrogen bonds. It has been found that values of bond-valence parameters decrease with increasing lanthanide atomic number in coordination compounds, and that they are smaller than the R(ij) parameters of inorganic compounds. As expected, the lanthanide-nitrogen bond-valence parameters are larger than lanthanide-oxygen bond-valence parameters. There are no obvious dependencies between the number of N atoms in the coordination sphere and the bond-valence parameter value.

Journal Article↗

PubMed2005

Conformationally restricted peptides as tools in opioid receptor studies.

The discovery of endogenous opioid peptides with their limited receptor selectivity more than two decades ago implicated their involvement in analgesia and initiated efforts to understand the molecular mechanisms underlying their action. Opioid peptides mediate their physiological and pharmacological effects through three major opioid receptor types (mu, delta, kappa), but the role of each of these receptors is not easy to distinguish. There has therefore, been an increasing need for potent and selective agonists and antagonists in this area. The incorporation of conformational constraints into analogs of biologically active peptides is a well-known approach for enhancing receptor selectivity and modulating efficacy. Conformational restriction has proven a valuable means for assessing disparities between the peptide binding characteristics at each of the opioid receptor types, since peptide analogs designed with appropriate conformational constraints possess the ability to adopt the conformation required for interaction at one receptor type but not another. In efforts to obtain better conformational integrity various conformationally restricted analogs of endogenous opioid peptides have been developed. In this paper we review the development of opioid analogs whose conformation was restricted either globally through different types of cyclization (such as amide bond formation, disulfide and monosulfide bridges, carbonyl and amine bridges) or locally, through incorporation of side-chain conformational constraints at a specific amino acid residue by synthesizing cyclic amino acids or constraining torsion angles by suitable substitutions. These two approaches have led to the development of potent and very selective agonists and antagonists at all three opioid receptor types.

Amino Acid Sequence↗

PubMed2004

New bond-valence parameters for lanthanides.

The bond-valence method, especially the valence-sum rule, is very useful for checking if the structures formed by trivalent lanthanides are correct. In this work bond-valence parameters (Rij), which connect bond valences and bond lengths, have been computed for a large number of bonds taken from the Cambridge Structural Database, Version 5.24 (2002) [Allen (2002). Acta Cryst. B58, 380-388]. The calculated values of bond-valence parameters for metal-organic compounds decrease with an increase in lanthanide atomic number; the Rij values are also smaller than bond-valence parameters calculated for inorganic compounds. A summary of bond-valence sums calculated for Rij given in this work and reported in the literature, and a functional correlation between lanthanide-oxygen distances and coordination number are presented.

Journal Article↗