Torrey Pines Institute for Molecular Studies

About: Torrey Pines Institute for Molecular Studies is a nonprofit organization based out in San Diego, California, United States. It is known for research contribution in the topics: Antigen & T cell. The organization has 2323 authors who have published 2217 publications receiving 112618 citations.

Protein profiling platform

Abstract: Methods and compositions are described for analyzing complex protein mixtures, such as proteomes, using activity-based probes. In particular, probes that specifically react with and bind to the active form of one or more target proteins are employed. Labeled peptides obtained from the labeled active target proteins can be used in screening and identification procedures, and can be related to the identity, presence, amount, or activity of active members of the desired target protein class. The methods and compositions described herein can be used, for example, to provide diagnostic information concerning pathogenic states, in identifying proteins that may act as therapeutic targets, and in drug discovery.

Arbitrarily primed PCR fingerprints resolved on SSCP gels

Abstract: Arbitrarily primed PCR methods (1), including RAPD (2), generate a reproducible fingerprint of DNA products from complex nucleic acids. Differences detected between fingerprints derived from different genomes have been used extensively as polymorphisms in genetic mapping (e.g., 3). Various strategies can be used to maximize the number of polymorphisms that are scored in each fingerprinting experiment. First, parents can be selected for the mapping population that have highly divergent genomes. Second, a large, but manageable, number of fragments in each fingerprinting experiment can be generated by using Stoffel fragment rather man Taq polymerase holoenzyme (4). Third, primers can be directed against sequences such as purine-pyrimidine microsatellite repeats that are intrinsically more polymorphic (5). Fourth, gel systems that detect more polymorphisms can be used, e.g., denaturing gradient gel electrophoresis (6). Another extremely simple method to increase the number of scorable polymorphisms would be to include single stranded conformation polymorphisms (SSCP) (7). This method could increase the number of scorable polymorphisms for two reasons. First, the two DNA strands from the same PCR product often run in different places on SSCP gels. This gives two opportunities to score a polymorphism whereas other gel systems afford only one such possibility for each polymorphism. Second, some PCR products from identical places in the two parental genomes may have internal sequence polymorphisms that will resolve as mobility differences on an SSCP gel. To test the utility of this approach we mapped polymorphisms in the mouse genome using the C57BL/6JXDBA and the A/JXC57BL/6J recombinant inbred mapping populations. Figure 1 shows a fingerprint for two parental strains separated on a denaturing polyacrylamide gel (lanes 1 and 2) and on an SSCP gel (lanes 3 and 4). Two conspicuous examples of resolved strands are labeled 'A' and 'B'. Figure 2 shows a fingerprint generated by a pair of primers used on genomic DNAs from a set of recombinant inbred lines. Strands derived from the same polymorphic PCR product could be assigned because of their completely concordant segregation patterns. The polymorphism indicated by an 'A' is known to be an SSCP polymorphism because it could not be scored on a denaturing gel (not shown). Length polymorphisms, labeled B, C, and D, could be scored at up to four places on the SSCP gel (Figure 2). In a series of five arbitrarily primed PCR experiments on recombinant inbred mouse genomes, the rate of detection of I 2

Systematic mining of generally recognized as safe (GRAS) flavor chemicals for bioactive compounds.

Abstract: Bioactive food compounds can be both therapeutically and nutritionally relevant. Screening strategies are widely employed to identify bioactive compounds from edible plants. Flavor additives contained in the so-called FEMA GRAS (generally recognized as safe) list of approved flavoring ingredients is an additional source of potentially bioactive compounds. This work used the principles of molecular similarity to identify compounds with potential mood-modulating properties. The ability of certain GRAS molecules to inhibit histone deacetylase-1 (HDAC1), proposed as an important player in mood modulation, was assayed. Two GRAS chemicals were identified as HDAC1 inhibitors in the micromolar range, results similar to what was observed for the structurally related mood prescription drug valproic acid. Additional studies on bioavailability, toxicity at higher concentrations, and off-target effects are warranted. The methodology described in this work could be employed to identify potentially bioactive flavor chem...