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.

Development and Optimization of Glaser–Hay Bioconjugations

Abstract: The prevalence of bioconjugates in the biomedical sciences necessitates the development of novel mechanisms to facilitate their preparation. Towards this end, the translation of the Glaser-Hay coupling to an aqueous environment is examined, and its potential as a bioorthogonal conjugation reaction is demonstrated. This optimized, novel, and aqueous Glaser-Hay reaction is applied towards the development of bioconjugates utilizing protein expressed with an alkynyl unnatural amino acid. Unnatural amino acid technology provides a degree of bioorthognality and specificity not feasible with other methods. Moreover, the scope of the reaction is demonstrated through protein-small molecule couplings, small-molecule-solid-support couplings, and protein-solid-support immobilizations.

The macrocyclic tetrapeptide [D-Trp]CJ-15,208 produces short-acting κ opioid receptor antagonism in the CNS after oral administration

Abstract: Background and Purpose Cyclic peptides are resistant to proteolytic cleavage, therefore potentially exhibiting activity after systemic administration We hypothesized that the macrocyclic κ opioid receptor (KOR)-selective antagonist [D-Trp]CJ-15,208 would demonstrate antagonist activity after systemic, that is, sc and oral (per os, p o), administration Experimental Approach C57BL/6J mice were pretreated with [D-Trp]CJ-15,208 sc or po before administration of the KOR-selective agonist U50,488 and the determination of antinociception in the warm-water tail-withdrawal assay The locomotor activity of mice treated with [D-Trp]CJ-15,208 was determined by rotorod testing Additional mice demonstrating cocaine conditioned place preference and subsequent extinction were pretreated daily with vehicle or [D-Trp]CJ-15,208 and then exposed to repeated forced swim stress or a single additional session of cocaine place conditioning before redetermining place preference Key Results Pretreatment with [D-Trp]CJ-15,208 administered sc or po dose-dependently antagonized the antinociception induced by ip administration of U50,488 in mice tested in the warm-water tail-withdrawal assay for less than 12 and 6 h respectively [D-Trp]CJ-15,208 also produced limited (<25%), short-duration antinociception mediated through KOR agonism Orally administered [D-Trp]CJ-15,208 dose-dependently antagonized centrally administered U50,488-induced antinociception, and prevented stress-, but not cocaine-induced, reinstatement of extinguished cocaine-seeking behaviour, consistent with its KOR antagonist activity, without affecting locomotor activity Conclusions and Implications The macrocyclic tetrapeptide [D-Trp]CJ-15,208 is a short-duration KOR antagonist with weak KOR agonist activity that is active after oral administration and demonstrates blood–brain barrier permeability These data validate the use of systemically active peptides such as [D-Trp]CJ-15,208 as potentially useful therapeutics

Interlaboratory comparison: liver spontaneous mutant frequency from lambda/lacI transgenic mice (Big Blue®) (II)

Abstract: Spontaneous mutant frequency in livers of two transgenic mouse strains, each carrying identical lambda shuttle vectors with a lacI target gene, was evaluated by two laboratories. These studies investigated variability in spontaneous mutant frequency between animals and as a function of the number of phage screened. Liver DNA was independently isolated from 7–11 week old C 57 BL 6 and B6C3F1 Big Blue® transgenic mice. At least 500 000 phage were screened for mutation at lacI for each animal using standardized assay procedures. In the two labs, the C 57 BL 6 liver spontaneous mutant frequency was 45 ± 9 × 10−6 and 41 ± 7 × 10−6. The B6C3F1 liver spontaneous mutant frequency was 42 ± 10 × 10−6 at one lab and 43 ± 12 × 10−6 and 41 ± 8 × 10−6 in two trials at the second lab. Mean mutant frequency data from both labs, calculated in increments of 100 000 plaque forming units (pfu) scored for each mouse strain, show stabilized mean mutant frequency and standard deviation after approximately 200 000–300 000 pfu screened. The frequency of spontaneous lacI mutants was reproducible both within and between labs and was comparable between the two transgenic mouse strains.