Conformational analysis of angiotensin I (AI) and II (AII) peptides has been performed through 2D 1 H-NMR spectroscopy in dimethylsulfoxide and 2,2,2-trifluoroethanol/H 2 O. The solution structural models of AI and AII have been determined in dimethylsulfoxide using NOE distance and 3 J HNHa coupling constants. Finally, the AI family of models resulting from restrained energy minimization (REM) refinement, exhibits pairwise rmsd values for the family ensemble 0.26 ± 0.13 Å , 1.05 ± 0.23 Å , for backbone and heavy atoms, respectively, and the distance penalty function is calculated at 0.075 ± 0.006 Å 2 . Comparable results have been afforded for AII ensemble (rmsd values 0.30 ± 0.22 Å , 1.38 ± 0.48 Å for backbone and heavy atoms, respectively; distance penalty function is 0.029 ± 0.003 Å 2 ). The two peptides demonstrate similar N-terminal and different C-terminal conformation as a consequence of the presence/absence of the His9-Leu10 dipeptide, which plays an important role in the different biological function of the two peptides. Other conformational variations focused on the side-chain orientation of aromatic residues, which constitute a biologically relevant hydrophobic core and whose inter-residue contacts are strong in dimethylsulfoxide and are retained even in mixed organic-aqueous media. Detailed analysis of the peptide structural features attempts to elucidate the conformational role of the C-terminal dipeptide to the different binding affinity of AI and AII towards the AT 1 receptor and sets the basis for understanding the factors that might govern free-or bounddepended AII structural differentiation.Keywords: angiotensin; NMR; renin-angiotensin system; solid phase peptide synthesis; solution structure.The octapeptide angiotensin-II (H-Asp-Arg-Val-Tyr-IleHis-Pro-Phe-OH, AII) is one of the oldest peptide hormones, known for its multiplicity of biological actions related to endocrine or connected to the central and peripheral nervous system. It is produced by the conversion of angiotensin-I (H-Asp-Arg-Val-Tyr-Ile-His-Pro-PheHis-Leu-OH, AI) to AII by the action of the angiotensin-I converting enzyme (ACE) of the vascular endothelium. AI is generated in the circulation by the action of rennin from the kidneys on its substrate, called alpha 2 -globulin or angiotensinogen, produced in the liver [1].AII is a potent pressor agent, which has a vital role in the regulation of blood pressure, in the conservation of total blood volume and salt homeostasis. Furthermore, it is involved in the release of alcohol dehydrogenase (ADH), cell growth and the stimulation of the sympathetic system. Several antagonists of AII are efficient antipressor agents. Inadequate functioning of the reninangiotensin system contributes substantially to the development of hypertension and cardiovascular and renal pathology (including left ventricular hypertrophy, structural alternations of the vasculature, neointima formation, nephrosclerosis, etc.) [2].Structure-activity relationships studies from several laboratories have revealed the to...

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