In the case of the PMB set, many pairs were generally related by high amcd values, probably because the changes corresponded to multiple amino acid exchanges, which cannot be realized on the complete molecules since each sequence analog requires a separate synthesis. Interestingly, one of the high amcd changes corresponds to a simple exchange of four aromatic aldehyde imines attached to the four diaminobutanoic acid residues, a reaction which would seem to be feasible (Figure ). This imine exchange is however accompanied by a mutation of a leucine residue to a phenylalanine.