Sets Of Libraries Research Articles

Identification of a potent analogue of Nazumamide A through iteration of combinatorial tetrapeptide libraries.

Five sets of N-acylated tetrapeptide libraries and sublibraries related to Nazumamide A have been prepared using 25 natural and unnatural amino acids. They were evaluated in antithrombin assay, in order to quantify inhibition at each step of the tetrapeptide sublibrary iteration. The studies led to the identification of 2,5-dihydroxybenzoyl-lysyl-isoleucyl-phenylalanyl-arginine as a novel inhibitor of thrombin and was found to be at least 25 times more potent than the natural tetrapeptide 2,5-dihydroxybenzoyl-arginyl-prolyl-isoleucyl-alpha-aminobutyric acid (NAZA).

Reference cDNA library facilities available from European sources.

cDNA libraries are the cornerstone of efforts to identify the relatively small regions of genomes that are responsible for biological effects. Gene hunter seeking candidate genes, via a variety of approaches, ultimately focus on the cloning, sequencing, and expression of cDNAs. Assistance is now available to researchers in the form of genome programs, whose initial goals include assembly of a complete collection of expressed sequences derived from the genome of interest. The concept of reference sets of cDNA libraries is that the aims of genome programs are served most effectively by different laboratories working on a common set of high-quality arrayed cDNA libraries, using different experimental approaches, thereby reducing unnecessary duplication of effort, and maximizing the amount of information that one set of resources can provide.

Proceedings of the schistosome genome project.

"The host-parasite relationship" is a vast and diverse research field which, despite huge human and financial input over many years, remains largely shrouded in mystery. Clearly, the adaptation of parasites to their different host species, and to the different environmental stresses that they represent, depends on interactions with, and responses to, various molecules of host and/or parasite origin. The schistosome genome project is a primary strategy to reach the goal; this systematic research project has successfully developed novel technologies for qualitative and quantitative characterization of schistosome genes and genome organization by extensive international collaboration between top quality laboratories. Schistosomes are a family of parasitic blood flukes (Phylum Platyhelminthes), which have seven pairs of autosomal chromosomes and one pair of sex chromosomes (ZZ for a male worm and ZW for a female), of a haploid genome size of 2.7 x 10(8) base pairs (Simpson et al. 1982). Schistosomes are ideal model organisms for the development of genome mapping strategies since they have a small genome size comparable to that of well-characterized model organisms such as Caenorhabditis elegans (100 Mb) and Drosophila (165 Mb), and contain functional genes with a high level of homology to the host mammalian genes. Here we summarize the current progress in the schistosome genome project, the information of 3,047 transcribed genes (Expressed Sequence Tags; EST), complete sets of cDNA and genomic DNA libraries (including YAC and cosmid libraries) with a mapping technique to the well defined schistosome chromosomes. The schistosome genome project will further identify and characterize the key molecules that are responsible for host-parasite adaptation, i.e., successful growth, development, maturation and reproduction of the parasite within its host in the near future.

Inhibitors of human heart chymase based on a peptide library.

We have synthesized two sets of noncleavable peptide-inhibitor libraries to map the S and S' subsites of human heart chymase. Human heart chymase is a chymotrypsin-like enzyme that converts angiotensin I to angiotensin II. The first library consists of peptides with 3-fluorobenzylpyruvamides in the P1 position. (Amino acid residues of substrates numbered P1, P2, etc., are toward the N-terminal direction, and P'1, P'2, etc., are toward the C-terminal direction from the scissile bond.) The P'1 and P'2 positions were varied to contain each one of the 20 naturally occurring amino acids and P'3 was kept constant as an arginine. The second library consists of peptides with phenylalanine keto-amides at P1, glycine in P'1, and benzyloxycarbonyl (Z)-isoleucine in P4. The P2 and P3 positions were varied to contain each of the naturally occurring amino acids, except for cysteine and methionine. The peptides of both libraries are attached to a solid support (pins). The peptides are evaluated by immersing the pins in a solution of the target enzyme and evaluating the amount of enzyme absorbed. The pins with the best inhibitors will absorb most enzyme. The libraries select the best and worst inhibitors within each group of peptides and provide an approximate ranking of the remaining peptides according to Ki. Through this library, we determined that Z-Ile-Glu-Pro-Phe-CO2Me and (F)-Phe-CO-Glu-Asp-ArgOMe should be the best inhibitors of chymase in this collection of peptide inhibitors. We synthesized the peptides and found Ki values were 1 nM and 1 microM, respectively. The corresponding Ki values for chymotrypsin were 10 nM and 100 microM. The use of libraries of inhibitors has advantages over the classical method of synthesis of potential inhibitors in solution: the libraries are reusable, the same libraries can be used with a variety of different serine proteases, and the method allows the screening of hundreds of compounds in short periods of time.

Duplication in Library Collections: What We Know and What We Need to Know

The great majority of academic libraries find themselves in a vast and often unmarked territory between two polar sets of goals and aspirations. These two poles could be represented by the model of the great research library, on the one hand, and the discount store, on the other. In choosing the first ideal, the library decides to acquire as broad a selection of research materials as possible, including infrequently used primary materials (census records, publications from limited editions, personal manuscripts, and unpublished pamphlets) in order that researchers may, at least in theory, find the collection all‐ or nearly all‐sufficient. Holders of this view point with pride to the contents of the catalog. At the other pole, the library sets out to be as responsive to demand as possible, to provide more and more of the materials which “move off the shelves” and, like the discount store, to discontinue stock items which are less popular than something more attractive which might replace them. Advocates of this view point with pride to the swarming circulation desk.