Inhibitory effect of a self-derived peptide on glucosyltransferase of Streptococcus mutans - Possible novel anticaries measures

Glucosyltransferase (GTF) plays an important role in the development of den tal caries. We examined the possible presence of self-inhibitory segments w ithin the enzyme molecule for the purpose of developing anticaries measures through GTF inhibition. Twenty-two synthetic peptides derived from various regions presumably responsible for insoluble-glucan synthesis were studied with respect to their effects on catalytic activity. One of them, which is identical in amino acid sequence to residues 1176-1194, significantly and specifically inhibited both sucrose hydrolysis and glucosyl transfer to glu can by GTF-I, Double-reciprocal analysis revealed that the inhibition is no ncompetitive. Scramble peptides, composed of the identical amino acids in r andomized sequence, had no effect on GTF-I activity. Furthermore, the pepti de is tightly bound to the enzyme once complexed, even in the presence of s odium dodecyl sulfate (SDS). Kinetic analysis using an optical evanescent r esonant mirror cuvette system demonstrated that the enzyme-peptide interact ion was biphasic. These results indicate that the peptide directly interact s with the enzyme with high affinity and inhibits its activity in a sequenc e-specific manner. This peptide itself could possibly be an effective agent for prevention of dental caries, although its effectiveness may be improve d by further modification.