Liquid-phase combinatorial synthesis.
A concept termed liquid-phase combinatorial synthesis (LPCS) is described. The central feature of this methodology is that it combines the advantages that classic organic synthesis in solution offers with those that solid-phase synthesis can provide, through the application of a linear homogeneous polymer. To validate this concept two libraries were prepared, one of peptide and the second of nonpeptide origin. The peptide-based library was synthesized by a recursive deconvolution strategy [Erb, E., Janda, K. D. & Brenner, S. (1994) Proc. Natl. Acad. Sci. USA 91, 11422-11426] and several ligands were found within this library to bind a monoclonal antibody elicited against beta-endorphin. The non-peptide molecules synthesized were arylsulfonamides, a class of compounds of known clinical bactericidal efficacy. The results indicate that the reaction scope of LPCS should be general, and its value to multiple, high-throughput screening assays could be of particular merit, since multimilligram quantities of each library member can readily be attained.
Han
H
H
Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
Wolfe
M M
MM
Brenner
S
S
Janda
K D
KD
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D016208:Databases, Factual; D004743:Enkephalin, Leucine / Q000032:analysis / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000032:analysis; D007202:Indicators and Reagents; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000276:immunology; D011092:Polyethylene Glycols; D012710:Serum Albumin, Bovine; D013329:Structure-Activity Relationship; D013449:Sulfonamides; D001615:beta-Endorphin / Q000032:analysis
D000911:Antibodies, Monoclonal; D000939:Epitopes; D007202:Indicators and Reagents; D009842:Oligopeptides; D013449:Sulfonamides; D012710:Serum Albumin, Bovine; D011092:Polyethylene Glycols; D004743:Enkephalin, Leucine; D001615:beta-Endorphin