NMR Structure of a Potent Small Molecule Inhibitor Bound to Human Keratinocyte Fatty Acid-Binding Protein

详细信息    查看全文

• 作者：Patricia A. McDonnell ; Keith L. Constantine ; Valentina Goldfarb ; Stephen R. Johnson ; Richard Sulsky ; David R. Magnin ; Jeffrey A. Robl ; Thomas J. Caulfield ; Rex A. Parker ; David S. Taylor ; Leonard P. A
• 刊名：Journal of Medicinal Chemistry
• 出版年：2006
• 出版时间：August 10, 2006
• 年：2006
• 卷：49
• 期：16
• 页码：5013 - 5017
• 全文大小：70K
• 年卷期：v.49,no.16(August 10, 2006)
• ISSN：1520-4804

文摘

The NMR structure is presented for compound 1 (BMS-480404) (K_i = 33 (±2) nM) bound to keratinocytefatty acid-binding protein. This article describes interactions between a high affinity drug-like compoundand a member of the fatty acid-binding protein family. A benzyl group ortho to the mandelic acid in 1occupies an area of the protein that fatty acids do not normally contact. Similar to that in the kFABP-palmitic acid structure, the acid moiety in 1 is proximal to R129 and Y131. Computational modeling indicatesthat the acid moiety in 1 interacts indirectly via a modeled water molecule to R109.