Design and synthesis of redox stable analogues of sunflower trypsin inhibitors (SFTI-1) on solid support, potent inhibitors of matriptase.
[structure: see text] 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 Ki 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.
Jiang
Sheng
S
Laboratory of Medicinal Chemistry, NCI, NIH, Frederick, Maryland 21702, USA.
Li
Peng
P
Lee
Sheau-Ling
SL
Lin
Cheng Yong
CY
Long
Ya-Qiu
YQ
Johnson
Michael D
MD
Dickson
Robert B
RB
Roller
Peter P
PP
D003500:Cyclization; D015195:Drug Design; D006368:Helianthus / Q000737:chemistry*; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014361:Trypsin Inhibitors / Q000737:chemistry*
D010455:Peptides; D015842:Serine Proteinase Inhibitors; D014361:Trypsin Inhibitors; D012697:Serine Endopeptidases; C485595:matriptase