Abstract
The antifreeze glycoproteins [AFGPs] are large molecules with molecule weights of 2.6-33 kDa, which
exhibit prominent antifreeze property and enable their organisms to survive in below the melting point of
water. While AFGPs have gained much attention in recent years, their availability is highly limited to the
isolation from natural resources. Although the total syntheses of AFGPs have been reported, the synthetic
methods have been limited due to their inherent gigantic molecular structures. Thus the development of
efficient synthetic alternatives of AFGPs with middle molecules is highly desirable. We herein design the
novel candidates of antifreeze molecules consisting of galactose-conjugated fluorinated and non-fluorinated
proline oligomers. They were designed based on the PP II helix with hydrophilic and lipophilic parts,
which could induce the potential antifreeze property. The target galactose-proline oligomers were
synthesized, and their physical properties were evaluated. Despite our expectation, the non-fluorinated
galactose-proline oligomers showed weak antifreeze activity in contrast to the fluorinated analogues. The
difference in antifreeze activity would be attributed to the fluorine gauche effect, which induces a different
conformation in fluorinated prolines from that of natural proline. These results suggest that the 3D structures
of the galactose-conjugated fluorinated and non-fluorinated proline oligomers are critical for their antifreeze
properties.
