The proline boronic acid dipeptides AlaboroPro (14), ProboroPro (15), and ValboroPro (16) are very potent inhibitors of the enzyme dipeptidyl peptidase IV (DPP IV or CD26), found on the surface of T-cells, and are a new class of immunosuppressants. The efficient synthesis of the free boronic acids as single enantiomers is described, and the absolute configuration determined. These compounds are known to lose DPP IV inhibitory activity in solution : this is shown to be due to the reversible formation of a cyclic species analogous to a diketopiperazine, containing a B-N bond. The cyclic compounds, both as the free boronic acids (17-19) and as the pinanediol esters (11-13), have been isolated and characterized by H-1 and B-11 NMR, and in one case by X-ray crystallography. The cyclization is pH dependent, with the open form favored at low pH, while the cyclic form predominates at neutral pH. Both the rate and extent of cyclization depend on the N-terminal amino acid. The rates of cyclization have been measured by H-1 NMR and shown to correlate with the decrease in DPP IV inhibitory activity. ValboroPro cyclizes more slowly, and to a lesser extent than AlaboroPro or ProboroPro, which is predicted to lead to greater immunosuppressive potency in vivo.