Toward the design of highly efficient, readily accessible peptide N-caps for the induction of helical conformations

A series of novel peptide N-caps was designed with an emphasis on ease of synthesis and an abundance of hydrogen bond acceptors. Different scaffolds based on sugars, cyclic hydrocarbons, and amino acids are developed with a variety of hydrogen bond acceptors including esters, carboxyls, amides and a sulfonic acid. The efficient use in solid-phase peptide synthesis was demonstrated by incorporating the N-caps to a resin-bound model peptide. Their differential helix nucleating power in aq. buffer was detd. by CD studies. Increases in peptide helicity to a significant extent are obsd., leading to a discussion of N-capping efficiency vs. ease of synthesis. The potential of the elaborated N-caps for the reversal of beta-sheet to alpha-helix conformations in the context of fibrillogenesis is discussed.