Protection of the Lactam Function of 2′-Deoxyinosine with A 2-(4-Nitrophenyl)-Ethyl Moiety

Abstract

The reaction of O-protected inosine with p-nitrophenyl ethanol under Mitsunobu conditions yields a mixture of the 1- and 0° -alkylated derivatives. 2′-Deoxyinosine protected on 0⁶ -, can be synthesized fairly easy from deoxyguanosine with a Mitsunobu reaction followed by reductive deamination.     

Ruddy turnstones Arenaria interpres rapidly build pectoral muscle after raptor scares

To cope with changes in the environment, organisms not only show behavioural but also phenotypic adjustments. This is well established for the digestive tract. Here we present a first case of birds adjusting their flight machinery in response to predation risk. In an indoor experiment, ruddy turnstones Arenaria interpres were subjected to an unpredictable daily appearance of either a raptor or a small gull (as a control). Ruddy turnstones experiencing threat induced by a flying raptor model, longer than after similar passage by the gull model, refrained from feeding after this disturbance. Pectoral muscle mass, but not lean mass, responded in a course of a few days to changes in the perceived threat of predation. Pectoral muscle mass increased after raptor scares. Taking the small increases in body mass into account, pectoral muscle mass was 3.6% higher than aerodynamically predicted for constant flight performance. This demonstrates that perceived risk factors may directly affect organ size.     

Both 2',3'-dideoxythymidine and its 2',3'-unsaturated derivative (2',3'-dideoxythymidinene) are potent and selective inhibitors of human immunodeficiency virus replication in vitro

2',3'-Dideoxythymidine (ddThd) and its 2',3'-unsaturated derivative 2',3'-dideoxythymidinene (ddeThd) are potent and selective inhibitors of human immunodeficiency virus (HIV) in vitro. When evaluated for their inhibitory effects on the cytopathogenicity of HIV in MT-4 cells, ddThd and ddeThd completely protected the cells against destruction by the virus at a concentration of 1 microM and 0.04 microM, respectively. In this aspect, ddeThd was about 5 times more potent than 2',3'-dideoxycytidine (ddCyd), one of the most potent and selective anti-HIV compounds now pursued for its therapeutic potential in the treatment of AIDS. ddThd and ddeThd also suppressed HIV antigen expression at 1 microM and 0.04 microM, respectively. Their selectivity indexes, as based on the ratio of the 50% cytotoxic dose to the 50% antiviral effective dose, were 120 (ddeThd) and greater than 625 (ddThd).     

The 2',3'-dideoxyriboside of 2,6-diaminopurine selectively inhibits human immunodeficiency virus (HIV) replication in vitro

The 2',3'-dideoxyriboside of 2,6-diaminopurine(ddDAPR) is, like 2',3'-dideoxyadenosine (ddAdo), a potent and selective inhibitor of human immunodeficiency virus (HIV) in vitro. The ddDAPR compound inhibits HIV antigen expression and HIV-induced cytopathogenicity in MT4 cells at a 50% effective dose (ED50) of 2.5-3.6 microM, as compared to 3.1-6.4 microM for ddAdo. Both compounds are endowed with a high selectivity index: 112 for ddDAPR and 139 for ddAdo. The 2',3'-unsaturated derivatives of ddDAPR and ddAdo, i.e. ddeDAPR and ddeAdo, are considerably more cytotoxic and less effective against HIV than the parental compounds. Like ddAdo, ddDAPR is only weakly inhibitory to the proliferation and DNA and RNA synthesis of a series of human B-lymphoblast, T-lymphoblast and T-lymphocyte cell lines. In contrast to ddAdo, which is rapidly deaminated by beef intestine adenosine deaminase at an initial velocity (Vi) of 145 mumol/mg protein/min, ddDAPR and ddeDAPR are poor substrates for the enzyme (Vi: 8 and 0.7 mumol/mg protein/min, respectively), which further contributes to the potential of ddDAPR as a chemotherapeutic agent against AIDS.     

The histone H1°/H5 variant and terminal differentiation of cells during development of Xenopus laevis

The maintenance of the differentiated condition is supposed to be associated with the presence of a histone of the H1(0)/H5 subclass. If the H1(0)/H5 variant has an important role in differentiation distinct from that of H1, it should display differential expression in time and position during development. Here we report that this prediction is verified during Xenopus laevis development, in which tadpoles exhibit a very characteristic, developmentally regulated pattern of histone H1(0)/H5 expression that is different for the derivatives of each embryonic germ layer. However, the pattern of appearance of this variant during development does not reflect a simple correlation between its presence and the state of differentiation. Therefore, these results are pertinent to current ideas on differentiation and the involvement of lysine-rich histones in the repression of eukaryotic genes.     

Molecular analysis of a reciprocal translocation t(5;11)(q11;p13) in a WAGR patient

Summary Most patients with the complex association aniridia — predisposition to Wilms' tumor (WAGR syndrome) present with a de novo constitutional deletion of band 11p13. We report a patient with WAGR syndrome and a reciprocal translocation between chromosomes 5 and 11 t(5;11)(q11;p13). High resolution banding cytogenetic analysis and molecular characterization using 11p13 DNA markers showed a tiny deletion encompassing the gene for CAT but sparing the gene for FSHB. This suggests that syndromes associated with apparently balanced translocations may be due to undetectable loss of material at the breakpoint(s) rather than to breakage in the gene itself.     

Incorporation of hexose nucleoside analogues into oligonucleotides: synthesis, base-pairing properties and enzymatic stability.

Oligonucleotides containing 1-(2,4-dideoxy-beta-D-erythro-hexopyranosyl)thymine (2) and 1-(3,4-dideoxy-beta-D-erythro-hexopyranosyl)thymine (3) were synthesized on a solid support using the phosphoramidite approach. The properties of these oligonucleotides were compared with the earlier reported characteristics of oligonucleotides containing 1-(2,3-dideoxy-beta-D-erythro-hexopyranosyl) thymine (1). The order in enzymatic stability of end-substituted oligonucleotides is 3 greater than 1 much greater than 2. The hybridization properties of the modified oligonucleotides are in reverse order: 2 much greater than 1 greater than 3.     

Polyphosphoinositol lipids inChlamydomonas eugametos gametes

InChlamydomonas eugametos gametes, phosphatidylinositol 4-phosphate (PtdInsP) and phosphatidylinositol 4,5-bisphosphate (PtdInsP₂) comprised 0.4 and 0.3% of the whole-cell phospholipids. They were concentrated in the plasma membrane around the cell body and were present in low concentrations in the flagellar membrane. When gametes were fed³²PO ₄ ^- , the label was rapidly incorporated into PtdInsP and PtdInsP₂ and only slowly incorporated into structural lipids such as phosphatidylethanolamine and phosphatidylglycerol. Similarly, when a pulse of³²PO ₄ ^- was chased with PO ₄ ^- , the label was rapidly lost from the polyphosphoinositol lipids but not from the structural lipids. The major fatty acids in the polyphosphoinositides were C-22 carbon polyenoic acids (70%). The significance of these results in relationship to intracellular signalling via inositol phosphates and Ca²⁺ is discussed.Abbreviations InsP₃ inositol 1,4,5-trisphosphate - mt^–/mt⁺ mating-type plus or minus - PtdA phosphatidic acid - PtdEtn phosphatidylethanolamine - PtdGro phosphatidylglycerol - PtdIns phosphatidylinositol - PtdInsP phosphatidylinositol 4-phosphate; - PtdInsP₂ phosphatidylinositol 4,5-bisphosphate - TCA trichloroacetic acid We thank Frank Schuring for Fig. 5A and Susan Kenter, Hans Kruisselbrink, Saskia Bijvank and Nelleke Corbett for their enthousiastic assistance.     

Potent and selective anti-HTLV-III/LAV activity of 2',3'-dideoxycytidinene, the 2',3'-unsaturated derivative of 2',3'-dideoxycytidine

2',3'-Dideoxycytidinene (ddeCyd), the 2',3'-unsaturated derivative of 2',3'-dideoxycytidine (ddCyd) is, like ddCyd itself, a potent and selective inhibitor of HTLV-III/LAV in vitro. This conclusion is based on the relatively high ratio of effective antiviral dose (0.3 microM) versus cell growth inhibitory concentration (20-35 microM) and the lack of any appreciable inhibitory activity against a series of non-oncogenic RNA and DNA viruses. Both compounds were considerably more inhibitory to human lymphoid cell lines than human nonlymphoid or murine cell lines. They were highly dependent on prior activation by deoxycytidine kinase to exert their anti-HTLV-III/LAV and cytostatic effects. In contrast with ddCyd, ddeCyd lost part of its anti-retrovirus effect upon prolonged incubation (10 days) with the virus-infected cells in culture.     

The distribution of aquatic oligochaetes in the fenland area of N.W. Overijssel (The Netherlands)

A synoptic study of the aquatic ecosystems in the Dutch province of Overijssel revealed the presence of 33 oligochaete taxa in the fendland area of N.W. Overijssel. The material was collected at 101 sampling sites in 1981. Oligochaetes were grouped by means of a normal and inverse cluster analysis. Although most oligochaetes are quite biquitous, differences in occurrence and abundance were observed and related to minor differences in environmental parameters.