Abstract: The present invention relates to novel methods for sequencing and mapping genetic markers in polynucleotide sequences using Type-IIs restriction endonucleases. The methods herein described result in the “capturing” and determination of specific oligonucleotide sequences located adjacent to Type-IIs restriction sites. The resulting sequences are useful as effective markers for use in genetic mapping, screening and manipulation.

Abstract: Libraries of unimolecular, double-stranded oligonucleotides on a solid support. These libraries are useful in pharmaceutical discovery for the screening of numerous biological samples for specific interactions between the double-stranded oligonucleotides, and peptides, proteins, drugs and RNA. In a related aspect, the present invention provides libraries of conformationally restricted probes on a solid support. The probes are restricted in their movement and flexibility using double-stranded oligonucleotides as scaffolding. The probes are also useful in various screening procedures associated with drug discovery and diagnosis. The present invention further provides methods for the preparation and screening of the above libraries.

Abstract: The present invention relates to novel methods for sequencing and mapping genetic markers in polynucleotide sequences using Type-IIs restriction endonucleases. The methods herein described result in the “capturing” and determination of specific oligonucleotide sequences located adjacent to Type-IIs restriction sites. The resulting sequences are useful as effective markers for use in genetic mapping, screening and manipulation.

Abstract: The present invention relates to novel methods for sequencing and mapping genetic markers in polynucleotide sequences using Type-IIs restriction endonucleases. The methods herein described result in the “capturing” and determination of specific oligonucleotide sequences located adjacent to Type-IIs restriction sites. The resulting sequences are useful as effective markers for use in genetic mapping, screening and manipulation.

Abstract: Means for simultaneous parallel sequence analysis of a large number of biological polymer macromolecules. Apparatus and methods may use fluorescent labels in repetitive chemistry to determine terminal manomers on solid phase immobilized polymers. Reagents which specifically recognize terminal manomers are used to label polymers at defined positions on a solid substrate.

Abstract: The present invention is generally directed to the evolution of new metabolic pathways and the enhancement of bioprocessing through a process herein termed recursive sequence recombination. Recursive sequence recombination entails performing iterative cycles of recombination and screening or selection to “evolve” individual genes, whole plasmids or viruses, multigene clusters, or even whole genomes. Such techniques do not require the extensive analysis and computation required by conventional methods for metabolic engineering.

Abstract: Means for simultaneous parallel sequence analysis of a large number of biological polymer macromolecules. Apparatus and methods may use fluorescent labels in repetitive chemistry to determine terminal manomers on solid phase immobilized polymers. Reagents which specifically recognize terminal manomers are used to label polymers at defined positions on a solid substrate.

Abstract: Novel inhibitors of metalloproteases, in particular collagenase-1 and stromelysin-1, are disclosed. Such compounds are useful in pharmaceutical compositions and methods for treating or controlling disease states or conditions which involve tissue breakdown, such as rheumatoid arthritis.

Abstract: Biotinylation peptides can be fused to other peptides or proteins of interest using recombinant DNA techniques to provide efficient methods for biotinylating the resulting fusion proteins in vivo or in vitro.

Abstract: A device and method for efficiently synthesizing diverse molecular products on substrates. A parent vessel 200 contains a suspension of substrates. The suspension is pressurized with argon and transferred to a plurality of reaction vessels 201-209 in one or more reaction vessel banks where monomer addition reactions take place. Optionally, the substrates may be tagged with a tag monomer. A vortexing motor 300 vortexes the contents of reaction vessels 201-209 during monomer addition reactions to enhance synthesis. After the desired monomer and/or tag monomer addition reaction, the suspension is pressurized with argon and transferred back to parent vessel 200 for mixing. Thereafter, the suspension may be pressurized with argon and reallocated among reaction vessels 201-209 for further synthesis.

Abstract: A general stochastic method for synthesizing random oligomers on particles is disclosed. A further aspect of the invention relates to the use of identification tags on the particles to facilitate identification of the sequence of the monomers in the oligomer.

Abstract: A random peptide library constructed by transforming host cells with a collection of recombinant vectors that encode a fusion protein comprised of a DNA binding protein and a random peptide and also encode a binding site for the DNA. binding protein can be used to screen for novel ligands. The screening method results in the formation of a complex comprising the fusion protein bound to a receptor through the random peptide ligand and to the recombinant DNA vector through the DNA binding protein.

Abstract: A general stochastic method for synthesizing random oligomers on particles is disclosed. A further aspect of the invention relates to the use of identification tags on the particles to facilitate identification of the sequence of the monomers in the oligomer.

Abstract: A general stochastic method for synthesizing random oligomers can be used to synthesize compounds to screen for desired properties. The use of identification tags on the oligomers facilitates identification of oligomers with desired properties.

Abstract: A random peptide library constructed by transforming host cells with a collection of recombinant vectors that encode a fusion protein comprised of a carrier protein fused to a random peptide through a proteolytic cleavage site can be used to identify ligands that bind to a receptor. The screening method results in the formation of a complex comprising the fusion protein bound to a receptor through the random peptide ligand, and the random peptide can easily be identified and analyzed by virtue of the carrier protein and associated proteolytic cleavage site.

Abstract: A device and method for efficiently synthesizing diverse molecular products on substrates. A parent vessel 200 contains a suspension of substrates. The suspension is pressurized with argon and transferred to a plurality of reaction vessels 201-209 in one or more reaction vessel banks where monomer addition reactions take place. Optionally, the substrates may be tagged with a tag monomer. A vortexing motor 300 vortexes the contents of reaction vessels 201-209 during monomer addition reactions to enhance synthesis. After the desired monomer and/or tag monomer addition reaction, the suspension is pressurized with argon and transferred back to parent vessel 200 for mixing. Thereafter, the suspension may be pressurized with argon and reallocated among reaction vessels 201-209 for further synthesis.

Abstract: Novel inhibitors of metalloproteases are disclosed. Such compounds are useful in pharmaceutical compositions and methods for treating or controlling disease states or conditions which involve tissue breakdown, such as rheumatoid arthritis.

Abstract: Peptides of 10 to 40 or more amino acid residues in length and having the sequence X3X4X5GPX6TWX7X8 (SEQ ID NO:252) where each amino acid is indicated by standard one letter abbreviation; X3 is C; X4 is R, H, L, or W; X.sub.5 is M, F, or I; X6 is independently selected from any one of the 20 genetically coded L-amino acids; X7 is D, E, I, L, or V; and X8 is C, which bind and activate the erythropoietin receptor (EPO-R) or otherwise act as an EPO agonist, and methods for their use.

Abstract: Biotinylation peptides can be fused to other peptides or proteins of interest using recombinant DNA techniques to provide efficient methods for biotinylating the resulting fusion proteins in vivo or in vitro.

Abstract: Novel inhibitors of metalloproteases, in particular collagenase-1 and stromelysin-1, are disclosed. Such compounds are useful in pharmaceutical compositions and methods for treating or controlling disease states or conditions which involve tissue breakdown, such as rheumatoid arthritis.