Imp
roved peptide-based inhibito
rs of human
rs/beta2.gif" BORDER=0 ALIGN="middle"> t
ryptase we
re discove
red using info
rmationgleaned f
rom t
ripeptide lib
ra
ry sc
reening and st
ructu
re-guided design methods, including f
ragment sc
reening.Ou
r effo
rts sought to imp
rove this class of inhibito
rs by
replacing the t
raditional Lys o
r A
rg P1 element.The optimized compounds display low nanomola
r potency against the mast cell ta
rget and seve
ral hund
red-fold selectivity with
respect to se
rine p
rotease off ta
rgets. Thus,
replacement of Lys/A
rg at P1 in a peptide-like scaffold does not need to be accompanied by a loss in ta
rget affinity.