Regioselective conjugation of chitosan with a laminin-related peptide, Tyr-Ile-Gly-Ser-Arg, and evaluation of its inhibitory effect on experimental cancer metastasis.
A conjugate from the YIGSR peptide and chitosan has been prepared on the basis of a regioselective modification strategy of chitosan, and its antimetastatic activity has been assayed. Chitosan was converted to its organosoluble derivative, 6-O-trityl-chitosan, in 3 steps, and then coupled with the peptide portion containing a spacer amino acid, Ac-Tyr-Ile-Gly-Ser-Arg-beta Ala-OH [beta Ala; beta-alanine]. The product was treated with CHCl2CO2H to afford the desired conjugate, Ac-Tyr-Ile-Gly-Ser-Arg-beta Ala-chitosan, which proved to inhibit the experimental lung metastasis of B16BL6 melanoma cells in mice at lower doses than the parent peptide.
Nishiyama
Y
Y
Department of Industrial Chemistry, Faculty of Engineering, Seikei University, Tokyo, Japan.
Yoshikawa
T
T
Kurita
K
K
Hojo
K
K
Kamada
H
H
Tsutsumi
Y
Y
Mayumi
T
T
Kawasaki
K
K
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002686:Chitin / Q000031:analogs & derivatives* / Q000737:chemistry; D048271:Chitosan; D007797:Laminin / Q000737:chemistry*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D009842:Oligopeptides / Q000737:chemistry*
D000970:Antineoplastic Agents; D007797:Laminin; D009842:Oligopeptides; C081571:tyrosyl-isoleucyl-glycyl-seryl-arginine; D002686:Chitin; D048271:Chitosan