Structure–Function Analysis of Urotensin II and Its Use in the Construction of a Ligand–Receptor Working Model
William A. Kinney Dr.
Drug Discovery Johnson & Johnson Pharmaceutical Research & Development Welsh and McKean Roads, Spring House, PA 19477-0776 (USA) Fax: (+1) 215-628-4985
Search for more papers by this authorHarold R. Almond, Jr. Dr.
Drug Discovery Johnson & Johnson Pharmaceutical Research & Development Welsh and McKean Roads, Spring House, PA 19477-0776 (USA) Fax: (+1) 215-628-4985
Search for more papers by this authorJenson Qi Dr.
Drug Discovery Johnson & Johnson Pharmaceutical Research & Development Welsh and McKean Roads, Spring House, PA 19477-0776 (USA) Fax: (+1) 215-628-4985
Search for more papers by this authorCharles E. Smith
Drug Discovery Johnson & Johnson Pharmaceutical Research & Development Welsh and McKean Roads, Spring House, PA 19477-0776 (USA) Fax: (+1) 215-628-4985
Search for more papers by this authorRosemary J. Santulli
Drug Discovery Johnson & Johnson Pharmaceutical Research & Development Welsh and McKean Roads, Spring House, PA 19477-0776 (USA) Fax: (+1) 215-628-4985
Search for more papers by this authorLawrence de Garavilla Dr.
Drug Discovery Johnson & Johnson Pharmaceutical Research & Development Welsh and McKean Roads, Spring House, PA 19477-0776 (USA) Fax: (+1) 215-628-4985
Search for more papers by this authorPatricia Andrade-Gordon Dr.
Drug Discovery Johnson & Johnson Pharmaceutical Research & Development Welsh and McKean Roads, Spring House, PA 19477-0776 (USA) Fax: (+1) 215-628-4985
Search for more papers by this authorDaniel S. Cho
Drug Discovery Johnson & Johnson Pharmaceutical Research & Development San Diego, CA 92121 (USA)
Search for more papers by this authorAnita M. Everson
Drug Discovery Johnson & Johnson Pharmaceutical Research & Development San Diego, CA 92121 (USA)
Search for more papers by this authorMark A. Feinstein
Drug Discovery Johnson & Johnson Pharmaceutical Research & Development San Diego, CA 92121 (USA)
Search for more papers by this authorPerry A. Leung
Drug Discovery Johnson & Johnson Pharmaceutical Research & Development San Diego, CA 92121 (USA)
Search for more papers by this authorBruce E. Maryanoff Dr.
Drug Discovery Johnson & Johnson Pharmaceutical Research & Development Welsh and McKean Roads, Spring House, PA 19477-0776 (USA) Fax: (+1) 215-628-4985
Search for more papers by this authorWilliam A. Kinney Dr.
Drug Discovery Johnson & Johnson Pharmaceutical Research & Development Welsh and McKean Roads, Spring House, PA 19477-0776 (USA) Fax: (+1) 215-628-4985
Search for more papers by this authorHarold R. Almond, Jr. Dr.
Drug Discovery Johnson & Johnson Pharmaceutical Research & Development Welsh and McKean Roads, Spring House, PA 19477-0776 (USA) Fax: (+1) 215-628-4985
Search for more papers by this authorJenson Qi Dr.
Drug Discovery Johnson & Johnson Pharmaceutical Research & Development Welsh and McKean Roads, Spring House, PA 19477-0776 (USA) Fax: (+1) 215-628-4985
Search for more papers by this authorCharles E. Smith
Drug Discovery Johnson & Johnson Pharmaceutical Research & Development Welsh and McKean Roads, Spring House, PA 19477-0776 (USA) Fax: (+1) 215-628-4985
Search for more papers by this authorRosemary J. Santulli
Drug Discovery Johnson & Johnson Pharmaceutical Research & Development Welsh and McKean Roads, Spring House, PA 19477-0776 (USA) Fax: (+1) 215-628-4985
Search for more papers by this authorLawrence de Garavilla Dr.
Drug Discovery Johnson & Johnson Pharmaceutical Research & Development Welsh and McKean Roads, Spring House, PA 19477-0776 (USA) Fax: (+1) 215-628-4985
Search for more papers by this authorPatricia Andrade-Gordon Dr.
Drug Discovery Johnson & Johnson Pharmaceutical Research & Development Welsh and McKean Roads, Spring House, PA 19477-0776 (USA) Fax: (+1) 215-628-4985
Search for more papers by this authorDaniel S. Cho
Drug Discovery Johnson & Johnson Pharmaceutical Research & Development San Diego, CA 92121 (USA)
Search for more papers by this authorAnita M. Everson
Drug Discovery Johnson & Johnson Pharmaceutical Research & Development San Diego, CA 92121 (USA)
Search for more papers by this authorMark A. Feinstein
Drug Discovery Johnson & Johnson Pharmaceutical Research & Development San Diego, CA 92121 (USA)
Search for more papers by this authorPerry A. Leung
Drug Discovery Johnson & Johnson Pharmaceutical Research & Development San Diego, CA 92121 (USA)
Search for more papers by this authorBruce E. Maryanoff Dr.
Drug Discovery Johnson & Johnson Pharmaceutical Research & Development Welsh and McKean Roads, Spring House, PA 19477-0776 (USA) Fax: (+1) 215-628-4985
Search for more papers by this authorGraphical Abstract
The salient structural features of urotensin II (U II) required for stimulation of its G-protein-coupled receptor were obtained from biological evaluation of synthetic derivatives of U II. This approach led to a plausible U-II–receptor complex (see picture), which inspired the installation of nonnatural amino acids in place of key residues. Notably, replacement of tyrosine with (2-naphthyl)-L-alanine resulted in a sixfold potency improvement compared to U II.
Supporting Information
Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2002/z18301_s.pdf or from the author.
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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