Synthesis and biological activity of cyclic peptide inhibitors of ribonucleotide reductase.

[formula: see text] A series of lactam-bridged peptide inhibitors (2-6) of mammalian ribonucleotide reductase (mRR) has been designed and synthesized on the basis of the heptapeptide N-AcFTLDADF (1), corresponding to the C-terminus of the R2 subunit of mRR. Inhibition studies revealed a direct relation between ring size and activity, with peptide 5 being 2.5 times more potent than peptide 1.