Selektiv S-geschützte Cysteinpeptide. IV. Zur Synthese von Cysteinpeptiden unter Verwendung der S-Ethylthio-Schutzgruppe. II

Selectively S-Protected Cysteine Peptides. IV Synthesis of Cysteine Peptides Using the S-Ethylthio Protecting Group. II Studying the problems of the selective sulphur protection in cysteine peptides, a model octapeptide from the sheep insulin A-chain was prepared by conventional synthesis using the S-ethylthio and the S-diphenylmethyl group. As consequence of the small acid stability of S-ethylthio protected cysteine peptides, the corresponding compounds were synthesized using the strong acid labile 2-(p-biphenylyl)-iso-propyloxycarbonyl(Bpoc) and the 2-phenyl-iso-propyloxycarbonyl(Ppoc) amino protecting group, respectively. Therefore a new synthesis of N-protected S-alkylthio cysteine derivatives 5 via N-unprotected compounds 4 was developed starting from S-guanylthio cysteine dihydrochloride 3 . The synthesis of the octapeptide Boc-Cys(SEt)-Cys(Dpm)-Ala-Gly-Val-Cys(SEt)-Ala-Leu-OBu^t 1 was carried out with the fragments Boc-Cys(SEt)-Cys(Dpm)-Ala-Gly-OH and TFA · H-Val-Cys(SEt)-Ala-Leu-OBu^t 12 by means of the DCCI/HOOBt coupling method. 12 was synthetisized step by step from the carboxyterminal end. The S-ethylthio group was completely stable during all synthetic steps including the deprotection of the N^α-Bpoc and N^α-Ppoc group, respectively. The cyclocystine octapeptide 2 , Boc-Cys-Cys(Dpm)-Ala-Gly-Val-Cys-Ala-Leu-OBu^t, was produced by treatment of 1 with an excess of HS CH₂ CH₂ OH followed by oxidation with I CH₂ CH₂ I.     

Blast wave simulation using AUTODYN2D: A parametric study

This paper is concerned with use of the hydrocode AUTODYN2D for the simulation of blast wave interactions with structures. A comprehensive parametric study is presented including an investigation of the effect of grid size on program output. Comparisons are made with well-established simple-geometry experimental data and with an experiment of more complex geometry. In both cases, results indicate that AUTODYN2D is a suitable tool for blast wave investigations.     

Induction of magnetic resonance-visible lipid in a transformed human breast cell line by tetraphenylphosphonium chloride

Proton magnetic resonance spectroscopy (1H MRS) and DNA flow cytometry were used to monitor the effects of the cationic lipophilic phosphonium salt and potential antineoplastic agent tetraphenylphosphonium chloride (TPP) on the transformed human breast cell line HBL-100. TPP treatment for 48 hr was cytostatic at low concentrations and cytotoxic at higher concentrations with an IC50 of 55 microM as measured by Trypan blue exclusion. At micromolar concentrations, TPP caused a significant increase in the methylene MR signal arising from mobile lipid as measured by the ratio of the lipid CH2 peak height to either the CH3 peak height (internal referencing) or the peak height for p-aminobenzoic acid (PABA) as an external reference in a co-axial capillary within the sample. Over the same concentration range, TPP caused a slowing of passage through S phase as demonstrated by a significant depletion of cells in G2/M phase with a concurrent but non-significant increase in cells in S. Time-dependent increases in MR-visible lipid were observed with 2 microM TPP treatment, and the removal of TPP from the culture medium caused no significant reduction in mobile lipid. Two-dimensional 1H-1H COSY spectra of TPP-treated HBL-100 cells revealed concentration-dependent increases in cross-peak volume ratios arising from lipid acyl chains relative to both internal (lysine, polyamines) and external (PABA) standards. Increases in choline and glycerophosphocholine cross-peak volume ratios were observed, indicating that the catabolism or rearrangement of phospholipids may be responsible for the observed MR-visible lipid increases.     

Molecular phylogeny of Fv1

Alleles at the Fv1 gene of inbred mice confer resistance to infection and spread of vertically or horizontally transmitted murine leukemia viruses (MuLV). The nucleotide sequence of Fv1 bears similarity to the gag of a human endogenous retrovirus, HERV-L, but is more closely related to the gag-coding sequence of a newly described class of HERV-L-related mouse endogenous retroviruses designated MuERV-L. Both observations suggest an origin of Fv1 from endogenous gag sequences. The molecular definition of Fv1 provided an opportunity to determine the phylogeny of the gene among wild mice and its relation to MuERV-L. PCR primers, chosen to include most of the coding region of Fv1 for both the n and b alleles, were used to amplify sequences from animals of the genus Mus, which were then sequenced. Closely related products were obtained from almost all animals examined that evolved after the separation from Rattus, in which the homologous gene was shown to be absent. A phylogenetic tree generated with Fv1 sequence data differs noticeably from that developed with sequence data from other genes. In addition, non-synonymous changes were found to be present twice as frequently as synonymous changes, a fact that departs from the standard behavior of a structural gene. These observations suggest that the Fv1 gene may have been subjected to possible horizontal transfers as well as to positive Darwinian selection.