BPTI backbone variants and implications for inhibitory activity.
Structural variants of BPTI were synthesized en route an enzymatic-chemical semisynthesis. The P1-P2 amide bond of the inhibitor molecule, which, as donor, contributes a hydrogen bond towards trypsin in the enzyme-inhibitor complex, was replaced by either a ketomethylene function or an ester bond yielding molecules with inhibitory activity. The two backbone-mutated BPTI derivatives showed increased dissociation constants of their respective trypsin complexes, obviously due to the lack of a single hydrogen-bond interaction in the enzyme-inhibitor complex.
Groeger
C
C
Department of Biochemistry, Faculty of Chemistry, Bielefeld University, Germany.
Wenzel
H R
HR
Tschesche
H
H
D007611:Aprotinin / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D006860:Hydrogen Bonding; D008958:Models, Molecular; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D014357:Trypsin / Q000187:drug effects*
D007611:Aprotinin; D014357:Trypsin