Details

Autor(en) / Beteiligte

• Maclean, Derek
• Schullek, John R.
• Murphy, Martin M.
• Ni, Zhi-Jie
• Gordon, Eric M.
• Gallop, Mark A.

Titel

Encoded Combinatorial Chemistry: Synthesis and Screening of a Library of Highly Functionalized Pyrrolidines

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 1997-04, Vol.94 (7), p.2805-2810

Ort / Verlag

United States: National Academy of Sciences of the United States of America

Erscheinungsjahr

1997

Quelle

MEDLINE

Beschreibungen/Notizen

• The application of a new encoding technology for drug discovery is described. A combinatorial library of mercaptoacyl pyrrolidines has been prepared on a beaded polymeric support. Each polymer bead carries one library constituent in association with an oligomeric ``tag,'' the structure of which is a record of the specific reagents from which that library member was prepared. After the ligands were solubilized, an array of such beads was screened for angiotensin-converting enzyme inhibitory activity, and the structures of active pyrrolidines were deduced by analysis of the associated tags at sub-picomole levels. Several extremely potent enzyme inhibitors were identified, many from multiple beads. The most potent inhibitor was found to have a Kiof 160 pM, ≈ 3-fold more active than captopril in the same assay. Direct comparison with interative deconvolution shows that the encoded screening strategy is a much more efficient means for extracting information from such compound collections, producing more data on a larger number of active structures.