NDLI: Chemical ecology: a view from the pharmaceutical industry.

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Intracellular Agrobacterium can transfer DNA to the cell nucleus of the host plant.

Could a nearby supernova explosion have caused a mass extinction?

Role of nitric oxide in control of prolactin release by the adenohypophysis.

FALL-39, a putative human peptide antibiotic, is cysteine-free and expressed in bone marrow and testis.

O2-sensitive K+ currents in carotid body chemoreceptor cells from normoxic and chronically hypoxic rats and their roles in hypoxic chemotransduction.

The chemistry of signal transduction.

Chemical ecology.

Different topoisomerase II antitumor drugs direct similar specific long-range fragmentation of an amplified c-MYC gene locus in living cells and in high-salt-extracted nuclei.

Sequential induction of 5-lipoxygenase gene expression and activity in Mono Mac 6 cells by transforming growth factor beta and 1,25-dihydroxyvitamin D3.

The Saccharomyces cerevisiae phosphatidylinositol-transfer protein effects a ligand-dependent inhibition of choline-phosphate cytidylyltransferase activity.

"Latent" inhibitory connections become functional during activity-dependent plasticity.

Functional coupling of Ca2+ channels and ryanodine receptors in cardiac myocytes.

Expression of an active glycosylated human gamma-glutamyl transpeptidase mutant that lacks a membrane anchor domain.

Cloning and functional expression of a rat kidney extracellular calcium/polyvalent cation-sensing receptor.

Expression of the wild-type p53 antioncogene induces guanine nucleotide-dependent stem cell division kinetics.

The chemistry of phyletic dominance.

Origin of the foraminifera. (Journal: Proceedings of the National Academy of Sciences of the United States of America Volume: 92 Issue: 1)

Forces of tertiary structural organization in globular proteins.

Comparative genomic analysis of tumors: detection of DNA losses and amplification.

Steroid/thyroid hormone receptor genes in Caenorhabditis elegans.

Site-specific recombination of a transgene in fertilized eggs by transient expression of Cre recombinase.

Optical mapping of site-directed cleavages on single DNA molecules by the RecA-assisted restriction endonuclease technique.

Supramolecular structure of the photosystem II complex from green plants and cyanobacteria.

Stereoelectronic effects of deoxyribose O4' on DNA conformation.

Urea unfolding of peptide helices as a model for interpreting protein unfolding.

The chemistry of social regulation: multicomponent signals in ant societies.

Increased cell surface expression and enhanced folding in the endoplasmic reticulum of a mutant erythropoietin receptor.

The chemistry of defense: theory and practice.

Structure, characterization, and expression of the rat oxytocin receptor gene.

Overexpression of plasminogen activator inhibitor 2 in human melanoma cells inhibits spontaneous metastasis in scid/scid mice.

Brain-derived neurotrophic factor promotes the survival of neurons arising from the adult rat forebrain subependymal zone.

Anti-human immunodeficiency virus 1 (HIV-1) activities of 3-deazaadenosine analogs: increased potency against 3'-azido-3'-deoxythymidine-resistant HIV-1 strains.

Altered behavior and long-term potentiation in type I adenylyl cyclase mutant mice.

The GTP-bound form of the yeast Ran/TC4 homologue blocks nuclear protein import and appearance of poly(A)+ RNA in the cytoplasm.

The chemistry of eavesdropping, alarm, and deceit.

Identification, activity, and structural studies of peptides incorporating the phorbol ester-binding domain of protein kinase C.

Cladistic analyses of combined traditional and molecular data sets reveal an algal lineage.

Structure and function in rhodopsin: the fate of opsin formed upon the decay of light-activated metarhodopsin II in vitro.

Cleavage of supercoiled plasmid DNA by autoantibody Fab fragment: application of the flow linear dichroism technique.

DNA damage and repair in telomeres: relation to aging.

Mapping the mouse ZP3 combining site for sperm by exon swapping and site-directed mutagenesis.

Erythrocyte lipids in triose-phosphate isomerase deficiency.

Rapid induction of tumor necrosis factor alpha in the cerebrospinal fluid after intracerebroventricular injection of lipopolysaccharide revealed by a sensitive capture immuno-PCR assay.

Basilar membrane resonance in the cochlea of the mustached bat.

Bidirectional interlocus concerted evolution following allopolyploid speciation in cotton (Gossypium).

A Staphylococcus aureus autolysin that has an N-acetylmuramoyl-L-alanine amidase domain and an endo-beta-N-acetylglucosaminidase domain: cloning, sequence analysis, and characterization.

Polydnavirus-facilitated endoparasite protection against host immune defenses.

Relation between oscillatory activity and long-range synchronization in cat visual cortex.

Can amino acid requirements for nutritional maintenance in adult humans be approximated from the amino acid composition of body mixed proteins?

Virus-mediated or transgenic suppression of a G-protein alpha subunit and attenuation of fungal virulence.

Axial skeleton homeosis and forelimb malformations in Hoxd-11 mutant mice.

Human immunodeficiency virus (HIV) antigens: structure and serology of multivalent human mucin MUC1-HIV V3 chimeric proteins.

DNA-dependent protein kinase activity is absent in xrs-6 cells: implications for site-specific recombination and DNA double-strand break repair.

A test of lattice protein folding algorithms.

DNA alterations detected in the progeny of paternally irradiated Japanese medaka fish (Oryzias latipes).

Binding of an invariant-chain peptide, CLIP, to I-A major histocompatibility complex class II molecules.

The chemistry of gamete attraction: chemical structures, biosynthesis, and (a)biotic degradation of algal pheromones.

Chemistry of sex attraction.

The chemistry of sexual selection.

Chemical signals in the marine environment: dispersal, detection, and temporal signal analysis.

Analysis of chemical signals by nervous systems.

Chemical ecology: a view from the pharmaceutical industry.

From mutation mapping to phenotype cloning.

Intrahelical ion pairs in intermediate filaments.

Screening for mutations by enzyme mismatch cleavage with T4 endonuclease VII.

The chemistry of poisons in amphibian skin.

The importance of intramolecular ion pairing in intermediate filaments.

Conformational implications of asparagine-linked glycosylation.

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Chemical ecology: a view from the pharmaceutical industry.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Caporale, L. H.
Description	Author Affiliation: Caporale LH ( Merck Research Laboratories, Rahway, NJ 07065.);
Abstract	Biological diversity reflects an underlying molecular diversity. The molecules found in nature may be regarded as solutions to challenges that have been confronted and overcome during molecular evolution. As our understanding of these solutions deepens, the efficiency with which we can discover and/or design new treatments for human disease grows. Nature assists our drug discovery efforts in a variety of ways. Some compounds synthesized by microorganisms and plants are used directly as drugs. Human genetic variations that predispose to (or protect against) certain diseases may point to important drug targets. Organisms that manipulate molecules within us to their benefit also may help us to recognize key biochemical control points. Drug design efforts are expedited by knowledge of the biochemistry of a target. To supplement this knowledge, we screen compounds from sources selected to maximize molecular diversity. Organisms known to manipulate biochemical pathways of other organisms can be sources of particular interest. By using high throughput assays, pharmaceutical companies can rapidly scan the contents of tens of thousands of extracts of microorganisms, plants, and insects. A screen may be designed to search for compounds that affect the activity of an individual targeted human receptor, enzyme, or ion channel, or the screen might be designed to capture compounds that affect any step in a targeted metabolic or biochemical signaling pathway. While a natural product discovered by such a screen will itself only rarely become a drug (its potency, selectivity, bioavailability, and/or stability may be inadequate), it may suggest a type of structure that would interact with the target, serving as a point of departure for a medicinal chemistry effort--i.e., it may be a 'lead.' It is still beyond our capability to design, routinely, such lead structures, based simply upon knowledge of the structure of our target. However, if a drug discovery target contains regions of structure homologous to that in other proteins, structures known to interact with those proteins may prove useful as leads for a medicinal chemistry effort. The specificity of a lead for a target may be optimized by directing structural variation to specificity-determining sites and away from those sites required for interaction with conserved features of the targeted protein structure. Strategies that facilitate recognition and exploration of sites at which variation is most likely to generate a novel function increase the efficiency with which useful molecules can be created.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	1
Volume Number	92
Language	English
Publisher	National Academy of Sciences
Publisher Date	1995-02-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Drug Design Ecology Genetic Variation Signal Transduction Animals Biological Evolution DNA Chemistry Metabolism DNA-Binding Proteins Hormones Nucleic Acid Conformation Protein Structure, Secondary Receptors, Cell Surface Physiology Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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