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Letter

Design and Synthesis of Redox Stable Analogues of Sunflower Trypsin Inhibitors (SFTI-1) on Solid Support, Potent Inhibitors of Matriptase

Supporting Info

Sheng Jiang,^†^‡ Peng Li,^†^§^‡ Sheau-Ling Lee, Cheng Yong Lin, Ya-Qiu Long,^† Michael D. Johnson,* Robert B. Dickson,^# and Peter P. Roller*^†;

Laboratory of Medicinal Chemistry, NCI, NIH, Frederick, Maryland 21702, and Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC 20057

Org. Lett., 2007, 9 (1), pp 9–12

DOI: 10.1021/ol0621497

Publication Date (Web): December 7, 2006

†

NCI, NIH.

‡

These authors contributed equally to the work.

Current address: Intra-Cellular Therapies, Inc., New York, 10032.

Georgetown University Medical Center.

Current address: Shanghai Institute of Materia Medica, Shanghai 201203, China.

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

In memory of Dr Robert B. Dickson

, proll@helix.nih.gov, ; , johnsom@georgetown.edu

Abstract

Matriptase is a member of the emerging class of type II transmembrane serine proteases. It was found that the sunflower trypsin inhibitor (SFTI-1), isolated from sunflower seeds, inhibits matriptase with a subnanomolar K_i of 0.92 nM. On the basis of this result, we designed and synthesized its proteolytically stable analogues, SFTI-2 and SFTI-3. SFTI-3 exhibited very good binding affinity to matriptase, and it was metabolically stable.

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Published In Issue January 04, 2007
Received August 30, 2006

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Letter

Design and Synthesis of Redox Stable Analogues of Sunflower Trypsin Inhibitors (SFTI-1) on Solid Support, Potent Inhibitors of Matriptase