Solid-phase synthesis of crystalline monellin, a sweet protein

The sweet protein, monellin, consists of two noncovalently associated polypeptide chains, the A chain of 44 amino acid residues and the B chain of 50 residues. The B chain was synthesized by the stepwise Fmoc solid-phase method in an overall yield of 6.2%. The synthetic B chain was combined with the synthetic A chain, which was left over from a previous work, to give monellin in a yield of 25.7%. The synthetic monellin was approximately 4000 times as sweet as sucrose, while the previously synthesized [Asn49, Glu50] B-chain monellin was also approximately 4000 times as sweet as sucrose. Exchanging Glu49 and Asn50 in the B chain did not affect the sweetness potency. Crystallization was performed by a vapor diffusion method.