Synthetic versions of seven naturally occurring omega-conopeptides were subjected to structural analyses in order to determine their disulfide bridge pattern. The method applied in this study uses a combination of amino-acid composition and peptide sequence analysis of various peptide fragments generated by different enzymatic digestions. A temperature modification in the Edman degradation cycles of a protein sequencer allowed the unambiguous detection of the cleavage of cystine residues. The appearance of the cystine residues in particular cycles of the sequence analysis was characteristic of one or several of the theoretically possible 15 isomers. In the case of multiple choices, possible isomers were further eliminated by the amino-acid and sequence analysis of peptide fragments generated by the enzymatic digestion. All synthetic peptides, SNX-111, -157, -159, -183, -185, -230 and -231, were found to have the same disulfide bridge pattern as determined for the naturally occurring omega-conopeptide G-VI-A, i.e. disulfide bridges between the half-cystines 1-16, 8-20 and 15-25 (using the amino-acid numbering of SNX-111).

Amino Acid Sequence↗

PubMedDate not supplied

Racism: is there a case for positive discrimination?

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China↗

PubMedDate not supplied

Pathways for activation of the ras-oncogene-encoded p21 protein.

The ras-oncogene-encoded p21 protein is known to cause a large number of human tumors. This protein differs from its normal counterpart protein, which is present in all eukaryotic cells, in that it contains a single amino acid substitution at critical positions in the polypeptide chain, such as at Gly 12, Gly 13, Ala 59, and Gln 61. Using computer-based molecular modeling, it has been found that one region of this protein that is a candidate for interacting with other intracellular proteins is the region from residues 35 to 47. In oocyte microinjection experiments, it was found that this peptide strongly inhibits the mitogenic effects of oncogenic (Val 12-containing)p21 but does not inhibit the cellular effects of activation of normal p21 protein. Furthermore, it has been shown that the cellular effects of oncogenic p21 protein can be completely inhibited by selectively blocking protein kinase C (PKC) with a highly specific inhibitor of this protein, CGP 41 251, a staurosporine derivative. This inhibitor, however, only weakly inhibits the effects of normal cellular ras-p21 protein. In addition, a photoaffinity-labeled p21 protein has been microinjected into NIH 3T3 fibroblasts and have isolated intracellular proteins of MW 35, 43 and 61 kda covalently bound to it. The 43 kda protein is the major one and appears to be critical to the functioning of the p21 protein. Our results suggest that oncogenic and normal p21 proteins utilize overlapping but distinct pathways; the oncogenic pathway can be blocked selectively and requires the activation of PKC and the presence of the 43 kda protein.

Amino Acid Sequence↗

PubMedDate not supplied

Suicide attempt due to metoclopramide-induced akathisia.

Akathisia as a side-effect of metoclopramide has received increasing attention in consultation-liaison psychiatry in recent years. A case of metoclopramide-induced akathisia resulting in a suicide attempt is reported in order to highlight the suffering of such patients and the factors that lead to misdiagnosis.

Adult↗