Synthesis and enzymatic evaluation of a P1 arginine aminocoumarin substrate library for trypsin-like serine proteases.
A method for the solid-phase synthesis of P1 arginine containing peptides via attachment of the arginine side-chain guanidine group is described. This procedure is applied to the preparation of a tetrapeptide, P1 arginine aminocoumarin PS-SCL. This library was validated by using it to determine the P4-P2 specificity for thrombin and comparing the results to the known thrombin subsite specificity. This is the first reported example of a PS-SCL library containing a P1 arginine.
Edwards
P D
PD
Department of Chemistry, AstraZeneca Pharmaceuticals, Wilmington, DE 19850-5437, USA. philip.edwards@astrazeneca.com
Mauger
R C
RC
Cottrell
K M
KM
Morris
F X
FX
Pine
K K
KK
Sylvester
M A
MA
Scott
C W
CW
Furlong
S T
ST
D001120:Arginine; D003374:Coumarins; D006801:Humans; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D019151:Peptide Library; D011487:Protein Conformation; D012697:Serine Endopeptidases / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013917:Thrombin / Q000378:metabolism*; D014357:Trypsin / Q000378:metabolism*
D003374:Coumarins; D009842:Oligopeptides; D019151:Peptide Library; D001120:Arginine; D012697:Serine Endopeptidases; D014357:Trypsin; D013917:Thrombin