We established MTAs with three of the four NIGMS-funded Chemical Methodologies & Library Developments (CMLD) (Boston University, University of Kansas, and University of Pittsburgh). These three centers alone have provided over 15,000 samples of known structure. Each CMLD has a distinct approach to library design, thus there is negligible overlap between their libraries. The MTP 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 Astana, Kazakhstan. MTP staff traveled to Kazakhstan on five occasions to develop this collaboration. We have organized plant collections focused on the 800 species endemic to Kazakhstan. To date, we have collected over 227 plant specimens; the plant extracts have been tested in the NCI 60 cell screen and prefractionated for testing in MTP screens. We have also collaborated with the Institute of Virology and Microbiology in Kazakhstan to screen 300 extracts of extremophilic actinomycetes from hypersaline and basic soils. 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. Another library is a collection of 700 plant extracts from the Brazilian cerrado, with Dr. Espindola of the University of Brasilia. Our ongoing collaboration with these laboratories has enabled us to receive a large collection of purified plant natural products as well. In a collaboration with the Blumberg Institute we have accessed 8,000 fungal extracts and 25,000 bacterial extracts from the Merck legacy natural products collection. New samples have also been received from a collaboration with the University of Istanbul, as well as hosting several Turkish scientists in the MTP. A new collaboration with the Moller lab in Copenhagen promises to add to our plant biotechnology based samples. We recently began to add prefractionated samples from the DTP to our screening set, replacing our in-house set. 150,000 samples have been added so far, with a similar number expected each year in the near future. Currently our storage system holds 246,085 tubes and 1454 plates. Over the past 10 years, the Chemical Diversity Development Section in the MTP 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. This system is currently under considerable renovation to improve its functionality and to add new capabilities.
Showing the most recent 10 out of 11 publications
