Structural features of angiotensin II which are important for biologic activity.

In summary, the aromatic ring of phenylalanine (COOH-terminus) is the key to the intrinsic activity with Tyr4, also involved in activation of a response. The NH2-terminal residue is a determinant of duration of action. The side chains of Tyr4 and His6 are key determinants for affinity, and the amino acids in the No. 1 and No. 2 position also contribute to receptor binding. Val3, Ile5, and Pro7 contain neutral side chains which probably establish and/or help maintain the appropriate distances among the key sidechains of Tyr4, His6, and Phe8. In other words, Val3, Ile5 (or Val), and Pro7 are key determinants of structural conformation.