title: Structure-guided design of peptide-based tryptase inhibitors.
abstract: Improved peptide-based inhibitors of human beta tryptase were discovered using information gleaned from tripeptide library screening and structure-guided design methods, including fragment screening. Our efforts sought to improve this class of inhibitors by replacing the traditional Lys or Arg P1 element. The optimized compounds display low nanomolar potency against the mast cell target and several hundred-fold selectivity with respect to serine protease off targets. Thus, replacement of Lys/Arg at P1 in a peptide-like scaffold does not need to be accompanied by a loss in target affinity.
authors: Celera Genomics, Inc., 180 Kimball Way, South San Francisco, California 94080, USA. mary.mcgrath@gilead.com
authors: Mary E
authors: ME
authors: McGrath
authors: Paul A
authors: PA
authors: Sprengeler
authors: Bernard
authors: B
authors: Hirschbein
authors: John R
authors: JR
authors: Somoza
authors: Isabelle
authors: I
authors: Lehoux
authors: James W
authors: JW
authors: Janc
authors: Erik
authors: E
authors: Gjerstad
authors: Michael
authors: M
authors: Graupe
authors: Angeles
authors: A
authors: Estiarte
authors: Chandru
authors: C
authors: Venkataramani
authors: Yang
authors: Y
authors: Liu
authors: Robb
authors: R
authors: Yee
authors: Joseph D
authors: JD
authors: Ho
authors: Michael J
authors: MJ
authors: Green
authors: Chang-Sun
authors: CS
authors: Lee
authors: Liang
authors: L
authors: Liu
authors: Vincent
authors: V
authors: Tai
authors: Jeffrey
authors: J
authors: Spencer
authors: David
authors: D
authors: Sperandio
authors: Bradley A
authors: BA
authors: Katz