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.

Mixture-based heterocyclic combinatorial positional scanning libraries: discovery of bicyclic guanidines having potent antifungal activities against Candida albicans and Cryptococcus neoformans.

Abstract: A mixture-based synthetic combinatorial library of more than 100,000 bicyclic guanidines was generated in a positional scanning format and assayed for activity against Candida albicans. Potent individual bicyclic guanidines were directly identified following the screening of the library. Time-kill curve studies indicated bactericidal activities for the individual bicyclic guanidines. These compounds also showed potent activity against Cryptococcus neoformans. These studies demonstrate the value of using mixture-based combinatorial positional scanning libraries made up of heterocyclic compounds for the rapid identification of novel classes of antifungal compounds.

Mutations in the p53 suppressor gene do not correlate with C-k-ras oncogene mutations in colorectal-cancer.

Abstract: Mutations in the p53 tumor suppressor gene have been analyzed in 196 colorectal tumors previously analyzed for mutations at codons 12 and 13 of the c-K-ras and N-ras oncogenes by a combination of Single Strand Conformation Polymorphism (SSCP) and Cycle Sequencing (CS) using total cellular RNA. Mutations were detected in 3 of 21 adenomas, 84 of 149 primary carcinomas, and 11 of 18 hepatic metastases. Over half of the tumors were homozygous for the mutant p53 allele at the mRNA level. Although deletions were detected in 5 tumors, missense mutations were the most frequent. The spectrum of 63 point mutations was heterogeneous, with all possible nucleotide substitutions ocurring at least once. No correlation was found between the spectrum of p53 gene mutations and the age, sex, race of the cancer patients or the anatomical localization of the tumors, although mutations were significantly more frequent in tumors of the distal colon. Mutations in the p53 gene did not correlate with mutations in the c-K-ras gene, indicating that colorectal cancer can develop through pathways independent not only of the presence of mutations in any of these genes but also of their cooperation.

Recombinant C345C and Factor I Modules of Complement Components C5 and C7 Inhibit C7 Incorporation into the Complement Membrane Attack Complex

Abstract: Complement component C5 binds to components C6 and C7 in reversible reactions that are distinct from the essentially nonreversible associations that form during assembly of the complement membrane attack complex (MAC). We previously reported that the approximately 150-aa residue C345C domain (also known as NTR) of C5 mediates these reversible reactions, and that the corresponding recombinant module (rC5-C345C) binds directly to the tandem pair of approximately 75-residue factor I modules from C7 (C7-FIMs). We suggested from these and other observations that binding of the C345C module of C5 to the FIMs of C7, but not C6, is also essential for MAC assembly itself. The present report describes a novel method for assembling a complex that appears to closely resemble the MAC on the sensor chip of a surface plasmon resonance instrument using the complement-reactive lysis mechanism. This method provides the ability to monitor individually the incorporation of C7, C8, and C9 into the complex. Using this method, we found that C7 binds to surface-bound C5b,6 with a K(d) of approximately 3 pM, and that micromolar concentrations of either rC5-C345C or rC7-FIMs inhibit this early step in MAC formation. We also found that similar concentrations of either module inhibited complement-mediated erythrocyte lysis by both the reactive lysis and classical pathway mechanisms. These results demonstrate that the interaction between the C345C domain of C5 and the FIMs of C7, which mediates reversible binding of C5 to C7 in solution, also plays an essential role in MAC formation and complement lytic activity.