A conjugate from a laminin-related peptide, Tyr-Ile-Gly-Ser-Arg, and chitosan: efficient and regioselective conjugation and significant inhibitory activity against experimental cancer metastasis

A laminin-related antimetastatic peptide was conjugated with chitosan, and antimetastatic activity of the peptide-chitosan conjugate was assayed. Chitosan was converted to its organosoluble derivative, 6-O-trityl-chitosan, in 3 steps, and then coupled with the peptide portion, Ac-Tyr-Ile-Gly-Ser-Arg-beta Ala-OH (beta Ala; beta-alanine), which contains a spacer amino acid at the carboxy-terminus. The product was treated with CHCl2CO2H to afford the desired conjugate, Ac-Tyr-Ile-Gly-Ser-Arg-beta Ala-chitosan. The peptide was introduced to every 6.3 glucosamine residues. The conjugate proved to have higher inhibitory activity against experimental lung metastasis of B16BL6 melanoma cells in mice than did the parent peptide.