We established of Material Transfer Agreements (MTA) with three of the four NIGMS-funded CMLDs (Boston University, the University of Kansas, and the University of Pittsburgh). These three centers have provided over 10,000 samples of known structure. Each CMLD has a distinct approach to library design, thus there is negligible overlap between their libraries. The MTL has subsequently entered into numerous agreements with other academic and industrial partners to increase the breadth of our libraries. Notable collaborations with traditional medicinal chemistry groups are with Prof. Gang Liu of Tsinghua University, and Prof. Roberto DiSanto of the University of Rome. Furthermore, we have obtained a number of focused compound sets, including LOPAC, the Glaxo Smith Kline kinase library, BioMol Natural Products, ICCB Known Bioactives, as well as a large series of synthetic compounds from DCTD, NCI. As part of a US State Department-funded threat reduction program, scientists at the former bioweapons (BW) facility in Stepnogorsk, Kazakhstan have been encouraged to explore non-BW scientific horizons. The program is conducted under the umbrella of the International Science and Technology Center (ISTC), in Almaty, Kazakhstan. MTL staff traveled to Kazakhstan on four occasions to develop this collaboration, which recently received notice of renewal for two more years. We have organized plant collections focused on the 800 species endemic to Kazakhstan. To date, we have collected over 177 plant specimens;the plant extracts have been tested in the NCI 60 cell screen and prefractionated for testing in MTL screens. Through collaboration with two Korean visiting scientists, Dr. Young Ho Kim (Chungnam National University, Daejon, Korea) and Dr. Ik Soo Lee (Chonnam National University, Gwangju, Korea), we obtained an extensive collection of Korean plant extracts. Our ongoing collaboration with these laboratories has enabled us to receive a large collection of purified plant natural products as well. A unique resource of fungal endophyte extracts has been obtained from Dr. Scott Strobel at Yale University. The endophytes have been cultured from Peruvian plants in an undergraduate class. The students arrange for biological testing at Yale and then isolate active natural products. Molecular testing at Yale ensures that the cultures are distinct. The laboratory of Dr. Ben Shen (Scripps Florida) specializes in the molecular genetics of actinomycetes, particularly non-ribosomal peptide and polyketide synthase systems. The Shen lab is also active in discovering means for stimulating expression of cryptic biosynthetic genes. Through collaboration with the Shen laboratory we have obtained access to hundreds of actinomycete extracts with well defined genetics, and a number of pure compounds. Compounds obtained from genetic manipulation of the biosynthetic pathways have provided structure-activity information in an MTL screening project. We have just entered into a collaboration with the Blumberg Institute which has given us access to the Merck legacy natural products collection. Currently our storage system holds 242,465 tubes and 1363 plates. Over the past 5 years, the CDDS has developed a customized web based assay and sample management system which allows our researchers to manage sample libraries, design assay plates and store and analyze bioassay data.
Showing the most recent 10 out of 11 publications
