PEPTIDE-ENCODING FOR STRUCTURE DETERMINATION OF NONSEQUENCEABLE POLYMERS WITHIN LIBRARIES SYNTHESIZED AND TESTED ON SOLID-PHASE SUPPORTS

A method of indirectly determining the structure of nonpeptidic or non sequenceable compounds that have been synthesized on individual partic les of solid support is described. The technique permits the parallel synthesis of a compound that is not susceptible to Edman degradation ( e.g., N-terminal-blocked peptide), or one containing components that c annot be identified by amino acid sequencing, together with a correspo nding ''coding'' peptide. Each coupling step in the assembly of the no nsequenceable compound is followed by the coupling of an amino acid to a different attachment site of the same carrier particle. whereby the amino acid unambiguously codes for the previously coupled building bl ock of the nonsequence able compound. The rationale is to enable the s equence determination of a biologically active compound that has been identified through the screening of a library of nonequenceable compou nds, by translating the sequence of its ''coding '' peptide, determine d by Edman degradation, into the structure of the active compound. The technique facilitates the construction and screening of nonpeptidic l ibraries for the discovery of important pharmaceutical compounds.