The purpose of the synthesis core facility is to provide the following to Projects II, III and IV: 1) routine synthesis of individual compounds of iterations from synthetic combinatorial libraries based on protocols produced during the development of those libraries in Project I; and 2) resynthesis of synthetic combinatorial libraries to replenish inventory. The use of trained technicians to perform this work is an efficient and cost effective way to accomplish this work, which is more routine than initial development of the library. The proposed core facility is an expansion of an existing facility located within the laboratories of Torrey Pines Institute for Molecular Studies, the applicant organization. This facility will be able to output between 300 to 500 compounds per month, depending on the complexity of the particular synthetic reaction schemes used, as well as provide analytical and purification services. The facility's primary function will be to synthesize individual defined compounds based on the results of screening the positional scan formatted synthetic combinatorial libraries. Secondary, functions will include the synthesis of sub-libraries based on the iterative deconvolution method as necessary, and synthesis and purification of individual compounds as necessary. It is expected that in the later portion of this program project the resynthesis of depleted libraries will be required. The synthesis core facility will be located at Torrey Pines Institute for Molecular Studies and will occupy 1,300 square feet of assigned space. Routine solid phase synthesis will be carried out using the simultaneous multiple synthesis technique developed by the principal investigator (tea- bag method). This laboratory contains a full complement of equipment necessary for organic synthesis. The available analytical/purification equipment include: 1H and 13C NMR, LC-MS, MALDI-MS, analytical and preparative HPLCs, and HPCE.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA078040-03
Application #
6300633
Study Section
Project Start
2000-03-27
Project End
2001-02-28
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
3
Fiscal Year
2000
Total Cost
$228,022
Indirect Cost
Name
Torrey Pines Institute for Molecular Studies
Department
Type
DUNS #
605758754
City
San Diego
State
CA
Country
United States
Zip Code
Pinilla, Clemencia; Appel, Jon R; Judkowski, Valeria et al. (2012) Identification of B cell and T cell epitopes using synthetic peptide combinatorial libraries. Curr Protoc Immunol Chapter 9:Unit9.5
Mitchell, Malcolm S; Lund, Teri A; Sewell, Andrew K et al. (2007) The cytotoxic T cell response to peptide analogs of the HLA-A*0201-restricted MUC1 signal sequence epitope, M1.2. Cancer Immunol Immunother 56:287-301
Hoesl, Cornelia E; Ostresh, John M; Houghten, Richard A et al. (2006) Solid phase synthesis of 3,4,7-trisubstituted 4,5,8,9-tetrahydro-3H-imidazo[1,2-a][1,3,5]triazepin-2(7H)-thiones and N-alkyl-4,5,7,8-tetrahydro-3H-imidazo[1,2-a][1,3,5]triazepin-2-amines. J Comb Chem 8:127-31
Nefzi, Adel; Ostresh, John M; Appel, Jon R et al. (2006) Identification of potent and highly selective chiral tri-amine and tetra-amine mu opioid receptors ligands: an example of lead optimization using mixture-based libraries. Bioorg Med Chem Lett 16:4331-8
Nefzi, Adel; Santos, Rodegar T (2005) Efficient approaches toward the solid-phase synthesis of new heterocyclic azoniaspiro ring systems: synthesis of tri- and tetrasubstituted 10-oxo- 3,9-diaza-6-azoniaspiro[5.5]undecanes. J Org Chem 70:9622-5
Berezovskaya, Olga; Schimmer, Aaron D; Glinskii, Anna B et al. (2005) Increased expression of apoptosis inhibitor protein XIAP contributes to anoikis resistance of circulating human prostate cancer metastasis precursor cells. Cancer Res 65:2378-86
Maynard, Jennifer; Petersson, Karin; Wilson, Dianne H et al. (2005) Structure of an autoimmune T cell receptor complexed with class II peptide-MHC: insights into MHC bias and antigen specificity. Immunity 22:81-92
Wang, Zhiliang; Cuddy, Michael; Samuel, Temesgen et al. (2004) Cellular, biochemical, and genetic analysis of mechanism of small molecule IAP inhibitors. J Biol Chem 279:48168-76
Nefzi, Adel; Ostresh, John M; Yu, Yongping et al. (2004) Combinatorial chemistry: libraries from libraries, the art of the diversity-oriented transformation of resin-bound peptides and chiral polyamides to low molecular weight acyclic and heterocyclic compounds. J Org Chem 69:3603-9
Becattini, Barbara; Sareth, Sina; Zhai, Dayong et al. (2004) Targeting apoptosis via chemical design: inhibition of bid-induced cell death by small organic molecules. Chem Biol 11:1107-17

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