Cyclic Aromatic Amino Acids with Constrained χ(1) and χ (2) Dihedral Angles.

The concept of topographic design of peptide neurotransmitters and hormones was pioneered by Hruby (1,2). When the design involved primarily constraint of the side chains of a peptide that has a well-defined backbone conformation, the term "topographic design on a stable template" was proposed (3). The side chain χ(1) of aromatic amino acids, such as Phe, Trp, Tyr, and His, can be constrained in either the gauche (-) or gauche (+) conformation by linking the nitrogen atom to the aromatic ring through a methylene bridge (Fig. 1). Fig. 1. Principle of side-chain constraint for Phe, Trp, and His.