111. Synthesis of a novel tricyclic dipeptide template and its incorporation into a cyclic peptide mimetic containing an NPNA motif

Article abstract of DOI:10.1002/hlca.19970800514

A novel tricyclic dipeptide template, formally derived by coupling (2S,4S)-4-aminoproline (Pro(NH₂)) and (S)-2-(carhoxymethyl)proline (Pro(CH₂COOH)) as a diketopiperazine, has been synthesized in a form suitable for solid-phase peptide synthesis using Fmoc chemistry. This template was incorporated into the cyclic molecule cyclo(-Ala¹-Asn²-Pro³- Asn⁴-Ala⁵-Ala⁶-Temp-) (Temp = template), whose conformation in H₂O was studied by NMR methods. Average solution structures derived by restrained simulated annealing point to a highly populated βI-turn within the Asn-Pro- Asn-Ala motif and also indicate which conformations are likely to be preferred by the template.