Department of Polar Sciences, University of Science and Technology, Incheon 406-840, KoreaReceived July 26, 2012, Accepted August 13, 2012Until now, few groups reported the antifreeze activity of cyclic glycopeptides; however, the tedious syntheticprocedure is not amenable to study the intensive structure activity relationship. A series of N-linked cyclicglycopeptoids and glycopeptide have been prepared to evaluate antifreeze activity as a function of peptidebackbone cyclization and methyl stereochemical effect on the rigid Thr position. This study has combined thecyclization protocol with solid phase peptide synthesis and obtained significant quantities of homogeneouscyclic glycopeptide and glycopeptoids. Analysis of antifreeze activity revealed that our cyclic peptidedemonstrated RI activity while cyclic glycopeptoids showed no RI activity. These results suggest that the subtlechanges in conformation and Thr orientation dramatically influence RI activity of N-linked glycopeptoids Key Words : Cyclic glycopeptide, Ice recrystallization inhibition, Solid phase synthesis, Cyclic glycopeptoidIntroductionAntifreeze glycoproteins (AFGPs) are essential materialsthat allow organism to thrive in harsh conditions. Fish,bacteria and other organisms produce AFGPs which havethe ability to inhibit the growth of ice, and thus allow themto survival in subzero temperature.