Action of Bauhinia bauhinioides synthetic peptides on serine proteinases.
The kallikrein inhibitor found in Bauhinia bauhinioides seeds (BbKI) differs from classical Kunitz plant inhibitors in the lack of disulfide bridges in its structure [Biochim. Biophys. Acta 1477 (2000) 64-74]. In this study, we examined whether structural properties may be involved in inhibitory specificity and, if so, whether those properties might be useful tools in designing compounds that interfere with enzyme activity. Peptides structurally related to the BbKI (RPGLPVRFESPLRINIIKE-NH(2)) reactive site were synthesized by solid-phase method and assayed for serine proteinase activity. The peptides RPGLPVRFESPLRINIIKE-NH(2), RPGLPVRFESPL-NH(2), and GLPVRFES-NH(2) were efficient tissue kallikrein inhibitors, with I(50) values of 0.54 microM, 0.87 microM, and 0.5mM, respectively. The lasting inhibitory effect was observed in incubation periods of up to 120 min. None of the studied peptides interfere with the activity of thrombin, factor Xa or trypsin, although the native protein BbKI is a potent trypsin inhibitor.
Departamento de Bioquímica, Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, Brazil.
Cristina I
CI
Cagliari
Fernanda P
FP
De Caroli
Adriana M
AM
Nakahata
Mariana S
MS
Araújo
Clovis R
CR
Nakaie
Misako U
MU
Sampaio
Claudio A M
CA
Sampaio
Maria Luiza V
ML
Oliva
D000595:Amino Acid Sequence; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000737:chemistry; D015951:Factor Xa / Q000737:chemistry*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D010940:Plant Proteins / Q000737:chemistry* / Q000145:classification*; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013917:Thrombin / Q000737:chemistry*; D014357:Trypsin / Q000737:chemistry*
C434623:BbKI protein, Bauhinia bauhinioides; D004791:Enzyme Inhibitors; D010455:Peptides; D010940:Plant Proteins; D012697:Serine Endopeptidases; D014357:Trypsin; D013917:Thrombin; D015951:Factor Xa