This paper reviews the preparation and use of soluble synthetic combin
atorial libraries (SCLs) made up of millions of peptide and nonpeptide
sequences for the identification of highly active individual compound
s. First presented in 1991, SCLs have been prepared in a number of dif
ferent lengths and formats, and are composed entirely of L-, D-, and u
nnatural amino acids. Also, existing peptide libraries have been chemi
cally transformed to yield large diversities of nonpeptidic compounds.
This review encompasses the published work from this laboratory using
SCLs for the identification of antigenic sequences recognized by mono
clonal antibodies, novel peptide agonists and antagonists to opioid re
ceptors, new trypsin inhibitors, novel antibacterials, and compounds t
hat inhibit melittin's hemolytic activity. SCLs offer a fundamental, p
ractical advance in the study of interactions between peptide and nonp
eptide sequences and their biochemical or pharmacological targets. (C)
1995 John Wiley & Sons, Inc.