In the quest for the elusive gamma-helix: homo-oligomers from 2-aminoadamantane-2-carboxylic acid

gamma-Turns (also termed C7 forms) are pseudo-cyclic structures that are stabilized by an intramolecular H-bond between the N(3)-H(3) and O(1)=C(1) groups. A series of contiguous gamma-turns generates a gamma- [or 2.2(7)-] helix. Such helical conformation, characterized by phi,psi = -70°,+70°, 2.2 residues per turn and an axial translation of 2.75 Å, although postulated more than 60 years ago, has never been experimentally authenticated yet.] Single and non-consecutive multiple gamma-turns are quite common in cyclo-4- and cyclo-5-peptides. Conversely, in linear peptides, gamma-turns have been rarely observed, and only one example of two consecutive gamma-turns has been crystallographically documented. This latter finding is far from surprising, because the shortest linear sequence potentially able to give rise to a two consecutive gamma-turns is a dipeptide acylated at the N-terminus and amidated at the C-terminus, i.e. the same main-chain length that allows the occurrence of a beta-turn conformation which is (in general) energetically favored over a double gamma-turn. Clearly, specific properties of the constituent amino acid residues are required for the onset of consecutive gamma-turns and eventually of a fully developed gamma-helix. In this connection, the results, including a number of crystal structures, of our ongoing investigation on peptides based on the severely hindered, C-alpha-tetrasubstituted alpha-amino acid Adm (2-aminoadamantane-2-carboxylic acid) will be reported.