Influence of the C-terminal substituent on the crystal-state conformation of Adm peptides

Abstract

The bis-functionalized diamondoid α-amino acid 2-aminoadamantane-2-carboxylic acid (Adm) has been used as the building block of four Nα-formyl homo-dipeptide alkylamide sequences via a solution-phase Ugi multicomponent reaction approach. The conformers of these peptides have been determined in the crystalline state by X-ray diffraction to distinguish the influences of the C-terminal substituent. One of the Adm peptides folds into an open and a hydrogen-bonded γ-turn geometry. Moreover, 3D-structures have been observed featuring two consecutive γ-turns in an incipient γ-helical structure, a significantly distorted nonhelical β-turn, as well as an S-shaped conformation with opposite helical screw senses. A significant topological variety is thus exhibited by the -Adm-Adm- sequences contingent on their C-terminal substituents, illustrating both the broad conformational potential and the need for further characterization of this sterically bulky residue in explorations of its ϕ, ψ space.