HYDROPHOBIC FORCES ARE RESPONSIBLE FOR THE FOLDING OF A HIGHLY POTENTNATRIURETIC PEPTIDE ANALOG AT A MEMBRANE MIMETIC SURFACE - AN NMR-STUDY

A conformational study by nmr spectroscopy was performed with the high ly active 28-residue hybrid natriuretic peptide analogue pBNP1 [M. Mim eault, A. De Lean, M. Lafleur, D. Bonenfant, and A. Fournier (1995) Bi ochemistry, Vol. 34, pp. 955-964], which consists of the cyclic peptid e core of pBNP32 and the N- and C-terminal exocyclic segments of rANP (99-126). In purely agueous solution pBNP1 exhibits random coil behavi or as evidenced by the almost complete absence of structurally signifi cant nmr observables. By contrast, elements of secondary structure eme rged upon the addition of dodecylphosphocholine micelles to the aqueou s sample. Nuclear Overhauser effect distance-restrained molecular dyna mics simulations in conjunction with torsional angle determinations pe rmitted the generation of a reasonable model of the lipid-bound confor mation of pBNP1. According to this model, pBNP1 adopts turn-like featu res in the cyclic and C-terminal regions of the peptide, but remains q uite flexible in the N-terminal segment. Two hydrophobic cores separat ed by a hydrophilic cleft were also evident in the generated structure . A mechanism is proposed whereby the hydrophobic interactions necessa ry to stabilize a folded structure of pBNP1 are facilitated by the pre sence of the membrane-like polar/apolar interface provided by the phos pholipid micelles. (C) 1997 John Wiley & Sons. Inc.