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l-3,4-Dehydroproline analogs of bradykinin

1978; Elsevier BV; Volume: 189; Issue: 1 Linguagem: Inglês

10.1016/0003-9861(78)90116-9

1096-0384

G. H. Fisher, D. I. Marlborough, James W. Ryan, Arthur M. Felix,

Click Chemistry and Applications

Three analogs of bradykinin (BK) containing l-3,4-dehydroproline (l-Δ3Pro) at positions 2, 3, or 7 of the BK sequence have been synthesized by the solid-phase technique and assayed for their effects on isolated smooth muscle tissues and on the systemic arterial blood pressure of rats. In these assays, (l-Δ3Pro2)-BK and (l-Δ3Pro3)-BK are as potent as BK itself, and each appears to be more resistant to enzymic degradation than BK itself during passage through the pulmonary circulation. (l-Δ3Pro7)-BK has approximately 25% of the potency of BK and appears to be more susceptible to pulmonary degradation than is BK. The circular dichroism (CD) spectra for the three analogs in water are similar in profile between 250 and 200 nm, although with different intensities, and more closely parallel the CD spectrum of BK in trifluoroethanol (TFE) than in water. The CD spectra in TFE show changes for all three analogs from the aqueous spectra. The TFE CD spectra of (l-Δ3Pro3)-BK and (l-Δ3Pro7)-BK are similar in profile to the spectrum of BK in TFE, whereas the spectrum of (l-Δ3Pro2)-BK is considerably different from that of BK. The spectroscopic changes can be interpreted in terms of a change in polyproline-like character or β-fold formation, presumably imposed by the greater rigidity of the dehydroproline ring.