Interaction of a peptidomimetic aminimide inhibitor with elastase.
The crystal structure of an aminimide analog of a dipeptide inhibitor of porcine pancreatic elastase bound to its target serine protease has been solved. The peptidomimetic molecule binds in the same fashion as the class of dipeptides from which it was derived, making similar interactions with the subsites on the elastase surface. Because aminimides are readily synthesized from a wide variety of starting materials, they form the basis for a combinatorial chemistry approach to rational drug design.
Peisach
E
E
Program in Biophysics, Brandeis University, Waltham, MA 02254, USA.
Casebier
D
D
Gallion
S L
SL
Furth
P
P
Petsko
G A
GA
Hogan
J C
JC
Ringe
D
D
D000595:Amino Acid Sequence; D000813:Anilides / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004151:Dipeptides / Q000737:chemistry / Q000378:metabolism*; D006834:Hydrazines / Q000737:chemistry / Q000378:metabolism*; D006860:Hydrogen Bonding; D008969:Molecular Sequence Data; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
D000813:Anilides; D004151:Dipeptides; D006834:Hydrazines; C094494:trifluoroacetyl-leucyl-(methyl benzyl aminimide)-4-isopropylanilide; C094478:trifluoroacetyl-leucyl-phenylalanyl-4-isopropylanilide; D010196:Pancreatic Elastase