Synthesis of the Library

The cyclic peptide was synthesised in such a manner that it was left attached to beaded synthesis resin. In schematic form, this can be represented as below:

The active loop region based on the natural protein inhibitory motif is shown in red, and includes the disulphide. This is linked (blue) to the beaded resin. The peptide retains activity whilst covalently attached.

Combinatorial Variation

At the positions marked X, Y, and Z in the diagram above, 20 different amino acid residues were introduced in a "one bead, one peptide" library. This results in 20 x 20 x 20 possible peptide sequences, but the synthesis is arranged so that each bead contains many copies of the same peptide sequence. The total synthesis, which involves hundreds of thousands of tiny beads, will produce all possible permutations of residues. The intention is that some combinations of sequence will be optimised for interaction with particular target proteins of interest.