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 nonsequenceable compounds that have been synthesized on individual particles 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 cannot be identified by amino acid sequencing, together with a corresponding "coding" peptide. Each coupling step in the assembly of the nonsequenceable 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 block of the nonsequenceable compound. The rationale is to enable the sequence determination of a biologically active compound that has been identified through the screening of a library of nonequenceable compounds, by translating the sequence of its "coding" peptide, determined by Edman degradation, into the structure of the active compound. The technique facilitates the construction and screening of nonpeptidic libraries for the discovery of important pharmaceutical compounds.
Nikolaiev
V
V
Selectide Corporation, Tucson, AZ 85737.
Stierandová
A
A
Krchnák
V
V
Seligmann
B
B
Lam
K S
KS
Salmon
S E
SE
Lebl
M
M
D000595:Amino Acid Sequence; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D017421:Sequence Analysis / Q000379:methods*
D010455:Peptides