No abstract

360ChemInform Abstract The structure of the title compound, the major component of the calichemicin complex (isolated from Micromonospora echinospora ssp. calichensis and known as LL-E33288 antibiotics) is investigated in part by chemical (derivatization, degradations etc.) and physical methods. It can be shown that the title compound consists of four glycosidic units, a hexasubstituted benzene moiety and an undefined C18H16NO4S3 unit. The exact configuration of the ethylamino sugar is unknown. In the following paper the structure of the undefined aglycone is reported.

361ChemInform Abstract Further chemical and physical investigations on the structure of the title compound, in addition to the results of the preceding paper, establish its complete structure as (I).

No abstract

Deorphanization of GPR54 receptor a decade ago led to the characterization of the kisspeptin receptor (Kissr) in mammals and the discovery of its major role in the brain control of reproduction. While a single gene encodes for Kissr in eutherian mammals including human, other vertebrates present a variable number of Kissr genes, from none in birds, one or two in teleosts, to three in an amphibian, xenopus. In order to get more insight into the evolution of Kissr gene family, we investigated the presence of Kissr in osteichthyans of key-phylogenetical positions: the coelacanth, a representative of early sarcopterygians, the spotted gar, a non-teleost actinopterygian, and the European eel, a member of an early group of teleosts (elopomorphs). We report the occurrence of three Kissr for the first time in a teleost, the eel. As measured by quantitative RT-PCR, the three eel Kissr were differentially expressed in the brain-pituitary-gonadal axis, and differentially regulated in experimentally matured eels, as compared to prepubertal controls. Subfunctionalisation, as shown by these differences in tissue distribution and regulation, may have represented significant evolutionary constraints for the conservation of multiple Kissr paralogs in this species. Furthermore, we identified four Kissr in both coelacanth and spotted gar genomes, providing the first evidence for the presence of four Kissr in vertebrates. Phylogenetic and syntenic analyses supported the existence of four Kissr paralogs in osteichthyans and allowed to propose a clarified nomenclature of Kissr (Kissr-1 to -4) based on these paralogs. Syntenic analysis suggested that the four Kissr paralogs arose through the two rounds of whole genome duplication (1R and 2R) in early vertebrates, followed by multiple gene loss events in the actinopterygian and sarcopterygian lineages. Due to gene loss there was no impact of the teleost-specific whole genome duplication (3R) on the number of Kissr paralogs in current teleosts.

Soluble enzymes from sage (Salvia officinalis) and tansy (Tanacetum vulgare), which catalyze the cyclization of geranyl pyrophosphate and the presumptive intermediate linalyl pyrophosphate to the (+) and (-) enantiomers, respectively, of 2-bornyl pyrophosphate, were employed to evaluate mechanistic alternatives for the pyrophosphate migration in monoterpene cyclization reactions. Separate incubation of [1-3H2,alpha-32P]- and [1-3H2,beta- 32P]geranyl and (+/-)-linalyl pyrophosphates with partially purified preparations of each enantiomer-generating cyclase gave [3H, 32P]bornyl pyrophosphates, which were selectively hydrolyzed to the corresponding bornyl phosphates. Measurement of 3H:32P ratios of these monophosphate esters established that two ends of the pyrophosphate moiety retained their identifies in the cyclization of both precursors to both products and also indicated that there was no appreciable exchange with exogenous inorganic pyrophosphate in the reaction. Subsequent incubations of each cyclase with [8,9-14C,1-18O]geranyl pyrophosphate and with (1E)-(+/-)-[1-3H,3-18O]linalyl pyrophosphate gave the appropriate (+)- or (-)-bornyl pyrophosphates, which were hydrolyzed in situ to the corresponding borneols. Analysis of the derived benzoates by mass spectrometry demonstrated each of the product borneols to possess an 18O enrichment essentially identical with that of the respective acyclic precursor. The absence of P alpha-P beta interchange and the complete lack of positional 18O isotope exchange of the pyrophosphate moiety are compatible with tight ion pairing of intermediates in the coupled isomerization-cyclization of geranyl pyrophosphate and establish a remarkably tight restriction on the motion of the transiently generated pyrophosphate anion with respect to its cationic terpenyl reaction partner.

No abstract

The NFKB-2 gene codes for an NF-B-related transcription factor containing rel-polyG-ankyrin domains. Chromosomal rearrangements of the NFKB-2 locus have been found in various types of lymphoid neoplasms, suggesting that they may contribute to lymphomagenesis. Rearrangements cluster within the 3-terminal ankyrin-encoding domain of the NFKB-2 gene and lead to the production of C-terminally truncated proteins which, in some cases, are fused to heterologous protein domains. In order to determine the functional consequences of these alterations, we have analyzed the subcellular localization, DNA binding, and transcriptional activity of two representative tumor-associated mutants in which the ankyrin domain is either terminally truncated (NFKB-2p85) or truncated and joined to an out-of-frame immunoglobulin C␣ domain (lyt-10C␣). Immunofluorescence studies performed on cells transfected with p85 or lyt-10C␣ expression vectors showed that both the abnormal proteins were constitutively localized in the nucleus. Immunoprecipitation analysis of UV-cross-linked DNA-protein adducts showed that p85 can bind B sites in its unprocessed form. Cotransfection of p85 or lyt-10C␣ expression vectors with B-driven reporter plasmids showed that both p85 and lyt-10C␣ have retained the ability to mediate transcriptional activation via heterodimerization with Rel-Ap65 but have lost the transrepression activity associated with homodimeric DNA binding. Furthermore, both p85 and lyt-10C␣ were capable of independent transactivation of B-reporter genes and this activity could not be further stimulated by Bcl-3. These findings indicate that the tumor-associated NFKB-2 proteins can override the main mechanisms regulating NFKB-2 function and act as constitutive transactivators without interaction with Rel-Ap65 or Bcl-3. These abnormal proteins may contribute to lymphomagenesis by determining a constitutive activation of the NF-B system and, in particular, of NFKB-2 target genes.The NFKB-2 gene (previously named , p50B/p97 [3], p55/p98 [20], and p49/p100 [30]) was independently identified via its involvement in a lymphoma-associated chromosomal translocation (24), its homology to NFKB-1 (20, 30), and its inducible expression in activated T cells (reference 3; for reviews, see references 13, 19, and 32). The NFKB-2 gene is expressed as a single 3.2-kb mRNA species and a 100-kDa primary translation product (p100) which, as NFKB-1 (5), contains an N-terminal DNA-binding rel domain, a poly(G) hinge, and a C-terminal ankyrin domain (7, 24). Analogous to NFKB-1, NFKB-2p100 represents a cytoplasmic precursor which, by proteolytic cleavage of the hinge region, is processed into an active molecule, p52, retaining the rel domain but losing the ankyrin domain (7, 21). NFKB-2p52 is found in the cytoplasm within complexes of 28,29) and IB (9) and can be found in the nucleus upon NF-B activation (7, 21). Although NFKB-2p52 has no intrinsic transcriptional activity, it can stimulate transcription by heterodimerizing with Rel-Ap65 or inhibit it by occupying B site...