Preferred conformation of the benzyloxycarbonyl‐amino group in peptides*

Abstract

Structural parameters, derived from X‐ray crystallographic data, have been compiled for 35 derivatives of amino acids, peptides, and related compounds, which contain the N‐terminal benzyloxycarbonyl (Z) group. The geometry of the urethane moiety of this end group is closely similar to that of the tert‐butoxycarbonyl (Boc) group, except for a relaxation of some bond angles because the Z group is sterically less crowded than the Boc group. For the same reason, the Z group has greater conformational flexibility. As a result, packing forces in the crystal may cause greater deformations of bond angles, resulting in larger variations of observed bond lengths and bond angles than in Boc‐peptide crystals. The aromatic rings of the Z end groups tend to stack in crystals. Conformational energy calculations indicate that most conformations of Z‐amino acid‐N' ‐methylamides and of corresponding Boc derivatives have similar dihedral angles and relative energies, i.e. the nature of the N‐terminal end group has little effect on the conformational preferences of the residue next to it. In particular, the computed fraction of molecules with a cisurethane (C‐N) bond is similar for the two derivatives: 0.51 and 0.42 in Boc‐Pro‐NHCH₃ and Z‐Pro‐NHCH₃, respectively, and 0.02 in the two Ala derivatives. There exist several computed conformations of Z‐Ala‐NHCH₃ and Z‐Pro‐NHCH₃ in which the phenyl ring and the C‐terminal methylamide group are close to each other. Because of favorable nonbonded interactions, such conformations are of low energy.