CONFORMATION OF CYCLIC-PEPTIDES - PRINCIPLE CONCEPTS AND THE DESIGN OF SELECTIVITY AND SUPERACTIVITY IN BIOACTIVE SEQUENCES BY SPATIAL SCREENING

The description of small cyclic peptide conformations can be simplifie d by substitution of the peptide bond for an olefinic structure, which then is converted into a single bond (for the E configuration) or a p seudo-CH2-group (for Z olefins). The resulting cycloalkane conformatio ns are related to the observed cyclic peptide structures. The individu al conformation, however, is strongly influenced by the array of chira lity in the peptide sequence. This can be used for a ''spatial screeni ng'' of biologically active peptide sequences. The procedure is demons trated on selective and highly active inhibitors for alpha(v) beta(3) integrins with a strong potential for development into anticancer drug s.