Abstract: Hybrid and novel polyketide synthases (PKSs) and polyketides are produced by use of a multiple vector system. The combinatorial possibilities offered by placing the various catalytic activities of PKS systems on separate vectors permits the construction of improved libraries of PKS and polyketides. In addition, polyketides can be produced in hosts that ordinarily do not produce polyketides by supplying, along with an expression system for the desired PKS, an expression system for holo acyl carrier protein (ACP) synthase.

Abstract: Recombinant DNA compounds that encode all or a portion of the oleandolide polyketide synthase are used to express recombinant polyketide synthase genes in host cells for the production of oleandolide, oleandolide derivatives, and polyketides that are useful as antibiotics and motilides.

Abstract: Yields of polyketides produced in host cells such as Streptomyces can be increased by coexpression of the ptpA gene. The introduction of recombinant vectors encoding ptpA and polyketide synthase genes is more efficient and does not require methyl-free DNA if the host cell is a restriction/methylation deficient strain, such as Streptomyces lividans K4-114, K4-155, or K27-39.

Abstract: Domains of epothilone polyketide synthase, and polynucleotides encoding therefor. Additionally, chimeric polyketide synthases that include domains, or subsets of domains, patterned on epothilone polyketide synthase. Methods to prepare epothilone in pharmaceutically useful quantitites are described, as are methods to prepare polyketide combinatorial libraries.

Abstract: Hybrid and novel polyketide synthases and polyketides are produced by use of a multiple vector system. The combinatorial possibilities offered by placing the various catalytic activities of PKS systems on separate vectors permits the construction of improved libraries of PKS and polyketides. In addition, polyketides can be produced in hosts that ordinarily do not produce polyketides by supplying, along with an expression system for the desired PKS, an expression system for holo ACP synthase.

Abstract: Human gene GC6 is expressed more abundantly in senescent cells than young cells. Isolated, purified, and recombinant nucleic acids and proteins corresponding to the human GC6 gene and its mRNA and protein products, as well as peptides and antibodies corresponding to the GC6 protein can be used to identify senescent cells, distinguish between senescent and young cells, identify agents that alter senescent gene expression generally and GC6 expression specifically; such agents as well as GC6 gene and gene products and products corresponding thereto can be used to prevent and treat diseases and conditions relating to cell senescence.

Abstract: Method and compositions are provided for the determination of telomere length and telomerase activity, as well as the ability to increase or decrease telomerase activity in the treatment of proliferative diseases. Particularly, primers are elongated under conditions which minimize interference from other genomic sequences, so as to obtain accurate determinations of telomeric length or telomerase activity. In addition, compositions are provided for intracellular inhibition of telomerase activity and means are shown for slowing or reversing the loss of telomeric repeats in aging cells.

Abstract: Method and compositions are provided for the determination of telomere length and telomerase activity, as well as the ability to inhibit telomerase activity in the treatment of proliferative diseases. Particularly, primers are elongated under conditions which minimize interference from other genomic sequences, so as to obtain accurate determinations of telomeric length or telomerase activity. In addition, compositions are provided for intracellular inhibition of telomerase activity.

Abstract: Method and compositions for increasing telomere length in normal cells can be used to increase the proliferative capacity of cells and to delay the onset of cellular senescence.

Abstract: Method and compositions are provided for the determination of telomere length and telomerase activity, as well as the ability to inhibit telomerase activity in the treatment of proliferative diseases. Particularly, primers are elongated under conditions which minimize interference from other genomic sequences, so as to obtain accurate determinations of telomeric length or telomerase activity. In addition, compositions are provided for intracellular inhibition of telomerase activity.

Abstract: A general stochastic method for synthesizing compounds can be used to generate large collections of tagged compounds that can be screened to identify and isolate compounds with useful properties.

Abstract: Telomerase activity in a sample can be measured using a two reaction protocol involving telomerase substrate and primer extension steps.

Abstract: An improved method for detecting and isolating differentially expressed mRNAs which comprises using first oligonucleotide primers for reverse transcription of mRNAs and both the first oligonucleotide primers and second oligonucleotide primers for amplification of the resultant cDNAs. The improvement of this method comprises providing first and second oligonucleotide primers with a length of at least 21 oligonucleotides. The method further comprises using a two-step PCR amplification, wherein non-stringent conditions are used for the first 1 to 4 cycles, and stringent conditions are used for the next 16 to 22 cycles. This highly reproducible method will permit the preparation of comprehensive catalogs of gene expression for any given cell type.

Abstract: Method and compositions are provided for the determination of telomere length and telomerase activity, as well as the ability to inhibit telomerase activity in the treatment of proliferative diseases. Particularly, primers are elongated under conditions which minimize interference from other genomic sequences, so as to obtain accurate determinations of telomeric length or telomerase activity. In addition, compositions are provided for intracellular inhibition of telomerase activity.

Abstract: Purified trypsin-sensitive agent or analog thereof, able to downregulate collagenase, PAI-1 and .beta.APP expression in senescent cells isolatable from culture medium having growing fibroblasts or U937 promyelocytic cells.

Abstract: Phsophonate esters can be synthesized in high yields by condensations of alcohols with methyl phosphonates followed by selective demethylation. The reaction is general, relativly insensitive to steric constraints of hindered phosphonic acids, and can also be carried out on a solid support to synthesize large collections of compounds to screen for pharmacological activity.

Abstract: A method and device for measuring the binding affinity of a receptor to a ligand. According to one aspect of the invention, arrays of polymers are synthesized or immobilized on a substrate (212). The array of polymers is exposed to a fluorescently-labelled receptor in solutions of varying concentration. The fluorescence intensity of the labelled receptor is measured by way of, e.g., a photon counter using a confocal microscope (316). Binding affinity is determined through analysis of the relationship between fluorescence intensity and the solution concentration of the receptor. On-rates are measured as a kinetic increase in surface fluorescence intensity, and the on-rate constant rate extracted from fits to the data.