The aminoxy acids NH 2 O–C– α HRCO– 2 H are much more easily obtained in the enantiomerically pure form than the analogous hydrazino acids NH 2 NH–C– α HRCO– 2 H, and it has been shown that the isosteric amidoxy ψ[CO–NH–O] and hydrazide ψ[CO–NH–NH] amide surrogates induce two quite similar γ‐like folded structures. An aminoxy acid can also be N ‐coupled to a peptide aldehyde to give the aldoxime ψ[CHNO–O] link or to a peptide ketone to form the ketoxime ψ[CRN O] link. The former can be further reduced into the hydroxylamine ψ[CH 2 NH–O] link which gives rise to reduced amidoxy peptides. The structural properties induced by these amide surrogates were studied, using IR and NMR spectroscopy, paying particular attention to the Z/E ‐isomerism of the oxime link. In order to investigate their inhibitory potency, the three amide surrogates were introduced in the Pro 3 ‐Val 4 and Val 4 ‐Ala 5 position of Z‐Ala 1 ‐Ala 2 ‐Pro 3 ‐Val 4 ‐Ala 5 ‐Ala 6 ‐NHiPr, a substrate which is cleaved in the Val 4 ‐Ala 5 position by human leukocyte elastase (HLE). The [Val 4 ψ[CONH–O–]Ala 5 ] analogue was still a substrate, while the [Pro 3 ψ[CONH–O–]Val 4 ] and [Val 4 ψ[CHN O –]Ala 5 ] pseudopeptides acted as HLE competitive inhibitors. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd.

An α-aminoxy acid residue has been introduced by liquid-phase procedures in a model dipeptide, by means of the amidoxy (CO–NH–O), oxime (CHN–O) and hydroxylamine (CH2–NH–O) pseudopeptide link. The structural properties induced by the three amide surrogates, which are not protonated at the physiological pH, have been studied in organic solution. In all three cases, the α-oxygen interacts with the adjacent amide NH to close a five-membered cycle. The amidoxy link gives rise to a very stable γ-like folded structure and the cis-oxime link to a β-like folded structure.

The pseudodipeptide, (S)-N-iso­propyl {[N-(pivaloyl)­pyrrol­idin-2-yl]­methyl­amino­oxy}acet­amide, C15H29N3O3, adopts a global extended conformation with the hydroxy­l­amine group in the g+/g− structure. The C-terminal amide NH interacts intramolecularly with the hydroxy­lamine O atom. Both NH bonds of each mol­ecule are hydrogen bonded to the C-­terminal amide carbonyl of a neighbouring mol­ecule.