The Replacement of His(4) in Angiotensin IV by Conformationally Constrained Residues Provides Highly Potent and Selective Analogues

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• 作者：Aneta Lukaszuk ; Heidi Demaegdt ; Debby Feytens ; Patrick Vanderheyden ; Georges Vauquelin ; Dirk Tourw
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：September 24, 2009
• 年：2009
• 卷：52
• 期：18
• 页码：5612-5618
• 全文大小：825K
• 年卷期：v.52,no.18(September 24, 2009)
• ISSN：1520-4804

文摘

The histidine residue in angiotensin IV was replaced by various conformationally constrained amino acids. The substitution of the His⁴−Pro⁵ dipeptide sequence by the constrained Trp analogue Aia−Gly, in combination with β²hVal substitution at the N-terminus, provided a new stable analogue H-(R)-β²hVal-Tyr-Ile-Aia-Gly-Phe-OH (AL-40) that is a potent ligand for the Ang IV receptor IRAP and selective versus AP-N and the AT1 receptor.