SYNTHESIS AND CHARACTERIZATION OF THE SWEETNESS-SUPPRESSING POLYPEPTIDE GURMARIN AND ENT-GURMARIN

The sweetness-suppressing polypeptide gurmarin isolated from the leave s of Gymnema sylvestre consists of 35 amino acid residues including th ree intramolecular disulfide bonds. Herein, the total chemical synthes is of gurmarin was performed by the stepwise fluoren-9-ylmethoxy-carbo nyl solid-phase method, the yield of reduced gurmarin being 1.9% based on the starting amino acid resin. Disulfide formation was carried out in the presence of a redox system of reduced glutathione/oxidized glu tathione to give gurmarin in a yield of 35.5%. The product was identic al to natural gurmarin by analytical reverse phase high performance li quid chromatography (RP-HPLC), mass spectroscopy (MS), and peptide map ping, and suppressed the responses to sucrose, D-glucose, and L-glucos e in a rat. The D enantiomer (all D-amino acid gurmarin) was also synt hesized, and was shown to be the mirror image of gurmarin. Interesting ly, the D enantiomer (ent-gurmarin) also suppressed the responses to s ucrose, D-glucose, and L-glucose in a rat. (C) 1996 John Wiley & Sons, Inc.