Synthetic Design The Balance of Novelty and Familiarity

Combinatorial Synthetic Design The Balance of Novelty and Familiarity 

School of Chemistry, University of Southampton, Southampton S017 IBJ, United Kingdom 

For recent general reviews on combinatorial libraries and design strategies, see Ref. 1. 

If a linear hexapeptide solution existed, it must have been present in Geysen s library (provided the synthesis worked perfectly, which is a separate issue). There are no additional umepresented sequences, and mathematically such libraries are called NP-complete (NP = non-deterministic polynomial time). Such NP-complete libraries are actually quite rare in combinatorial chemistry. Although there are infinite numbers of peptides, for Geysen s epitope mapping, he needed to examine only natural amino acids. This reduces the complexity for a sequence of length n to 20 , a number that increases exponentially with n but nevertheless remains finite. 

Among peptide libraries today, such NP-complete sets are uncommon. It is often profitable to expand the monomer set to include unnatmal amino acids, thus once again leading to infinite possibilities. Even within the narrower context of natural peptides, the complete set of 20 amino acids is seldom employed in synthetic libraries. In Houghten s example above, both cysteine and tryptophan were omitted to avoid problems due to oxidative side reactions, while others often substitute 

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