Aza-peptides. III. Experimental structural analysis of aza-alanme and aza-asparagine-containing peptides

To determine the structural perturbations induced by the CαH→Nα exchange in aza-peptides, we have examined by H NMR and IR spectroscopy various derivatives of the aza-analogues of alanine, aspartic acid and asparagine in different organic solvents with increasing polarity. Their general formulas are: R'-AzXaa-NR²R³, R'-Pro-AzXaa-NR²R³ and R-AzXaa-Pro-NR²R³ (where AzXaa denotes the aza-analogue of the amino acid residue Xaa = Ala, Asp, Asn; R = Boc, Z; R², R³= H, Me, iPr). The aza-analogue of an amino acid residue appears to be a strong p-turn-inducing motif, and the AzAsn carboxamide side-chain is capable of interacting, as a proton donor, with the preceding peptide carbonyl group.     

Aza-peptides II. X-Ray structures of aza-alanine and aza-asparagine-containing peptides

In order to determine the structural consequences of the N^x/C^xH exchange in aza-peptides, we have solved the crystal molecular structures of some derivatives containing the aza-analogue of asparagine [Z-AzAsn(Me)-NMe₂ (1), Z-AzAsn(Me)-Pro-NHiPr (2) and Piv-Pro-AzAsn(Me)-NHiPr (5), aspartic acid [Z-AzAsp(OEt)-Pro-NHiPr (3) and alanine (Boc-AzAla-Pro-NHiPr (4), by using X-ray diffraction. They reveal that the α-nitrogen accommodates a pyramidal (1–4) or planar (5) structure depending on the sequence. When pyramidal, the α-nitrogen assumes the R (D-like) chiralily. All of the derivatives but 1 adopt either a β₁-folded (2–4) or β_II-folded (5) structure in which the (AzAsn)N^δH bond is intramolecularly hydrogen-bonded to the α-nitrogen. © Munksgaard 1997.