Acta chemica Scandinavica. Series B: Organic chemistry and biochemistry最新文献

Using well-established solid-phase techniques, three new analogues of arginine-vasopressin (AVP) were synthesized. In these the glutamine residue in position 4 was replaced with an additional arginine. The new analogues were: [Arginine4]arginine-vasopressin ([Arg4]AVP), [2-thiopropionic acid1,arginine4]arginine-vasopressin (d[Arg4]AVP) and [1-thiocyclohexaneacetic acid1,arginine4]arginine-vasopressin (d(CH2)5[Arg4]AVP). [Arg4]AVP showed about the same antidiuretic activity as AVP but had only about 40% of its pressor activity. Unexpectedly, deamination caused a drop in the antidiuretic activity to about 50%. d(CH2)5[Arg4]AVP had practically negligible antidiuretic and low pressor effects.

The phenylhydrazone of N-[D-fructosyl-(1)]-L-valine (1-deoxy-L-valine-D-fructose) was synthesized. The hydrazone was shown to exist in open form in basic solution and in closed form in acidic solution. The findings have bearings upon the discussion of the reaction of human haemoglobin A1c with phenylhydrazine.

35S-Labelled heparan sulfates derived from the culture medium (extracellular), a trypsinate of the cells (pericellular) and the cell residue (intracellular) of quiescent normal, proliferating normal or SV40-transformed 3T3 cells were analyzed for charge heterogeneity, by ion exchange chromatography and for self-affinity, by chromatography on heparan sulfate-agarose gels. Quiescent normal cells retained most of their heparan sulphate intra- or pericellularly. The surface-exposed material was charge heterogeneous and had a strong affinity for heparan sulfate. In cultures of growing cells and transformed cells most of the heparan sulfate was found in the medium. The heparan sulfate retained on the surface or growing cells had a lower self-affinity than did the corresponding material from normal and transformed cells. Although cell surface heparan sulfates from transformed cells showed affinity for a matrix substituted with the total heparan sulfate pool, the affinity for one particular subtype was much less pronounced or non-existent.

5-Ethyl-2'-deoxyuridine (5EtdUrd) is a biologically active thymidine analogue. The cytotoxicity of 5EtdUrd was investigated with seven established human leukemia cell lines as well as with human peripheral blood PHA-stimulated lymphocytes. All types of leukemia cells were susceptible to the toxicity of 5EtdUrd as assayed with a [U-14C]-L-leucine incorporation system developed for this study. A 50% inhibition of leucine incorporation in 3-day cultures was induced by 1.3-3.8 microM 5EtdUrd with leukemic cells, but the concentration required to induce similar inhibition with PHA-stimulated lymphocytes was approximately was approximately 100-fold. The toxicity of 5EtdUrd seemed to require active DNA synthesis, since the inhibition of leucine incorporation became obvious only after the first 24 hours of culture. The DNA incorporation studies were based on a new isotopically labeled 5EtdUrd derivative, [2-14C]5EtdUrd, synthesized for this study in our laboratory. It was demonstrated for the first time that most of the radioactivity derived from [2-14C]5EtdUrd in DNA was in 5-ethyluracil. 5EtdUrd has a powerful antileukemic potency in vitro. Its effects against human leukemia in vivo remain to be tested.

The highly mutagenic title compound (MeIQx) was prepared in 21% overall yield from 4-fluoro-o-phenylenediamine. The 3,7-dimethyl isomer may be obtained as a minor by-product. The 14C-label was introduced in the last step through cyclization with [14C]cyanogen bromide. An alternative synthesis of MeIQx from p-fluoroaniline avoided the separation of isomers but gave poorer yield.

5-Hydroxymethyl-2'-deoxyuridine is a biologically active thymidine analogue. This investigation was aimed at characterizing the cytotoxicity of 5-hydroxymethyl-2'-deoxyuridine and its incorporation into DNA. Fifty percent inhibition of cellular proliferation, assessed by incorporation of [U-14C]-L-leucine in vitro, was caused by 1.7-5.8 X 10(-5) incorporation of [U-14C]-L-leucine in vitro, was caused by 1.7-5.8 X 10(-5) M 5-hydroxymethyl-2'-deoxyuridine in seven human leukemia cell lines. Higher concentrations of 5-hydroxymethyl-2'-deoxyuridine, i.e. 6-8 X 10(-5) M, were required for a comparable inhibition in human PHA-stimulated peripheral blood lymphocytes. A new synthesis procedure for [2-14C]5-hydroxymethyl-2'-deoxyuridine was developed. The net incorporation of [2-14C]5-hydroxymethyl-2'-deoxyuridine into DNA of hematopoietic cells was low. The possibility of a repair mechanism for 5-hydroxymethyluracil bound to DNA is discussed.

Secondary metabolites from marine bryozoans are reviewed. Two ctenosome bryozoans are dealt with, one, Alcyonidium gelatinosum containing a sulfoxonium ion acting as hapten in an allergic contact dermatitis and the other, Zoobotryon verticillatum yielding bromogramines. Five cheilostome bryozoans have given rise to the isolation of unique secondary natural products. Bugula neritina is the source of the antineoplastic bryostatins and Bugula purple while Flustra foliacea have yielded an array of bromoindole alkaloids and a brominated quinoline. Chartella papyracea also have bromoindole alkaloids while Sessibugula translucens have ecological active bipyrroles. A biological active xanthine derivative has been reported from Phidolopora pacifica. The structure and chemistry of these compounds are discussed as are their origin, function and biological activity.