Design and Synthesis of Antifreeze Glycoproteins and Mimics

Abstract

Antifreeze glycoproteins are an important class of biological antifreezes that have potential applications in many areas of medicine, agriculture and industry in which ice crystal growth is damaging. While the synthesis of antifreeze glycoproteins as pure glycoforms has recently been achieved by using ligation and polymerisation strategies, the routine production of large quantities of pure glycoforms remains challenging. A range of C-linked analogues that are readily produced by solid-phase synthesis have delivered novel compounds that are not biological antifreezes, but are potent, non-cytotoxic, ice-recrystallisation inhibitors. Structure-activity studies, the identification of cyclic antifreeze glycoproteins and conformational studies have provided further insight into the requirements for antifreeze activity. These results, coupled with significant advances in approaches to the routine synthesis of different glycoproteins and mimics, present opportunities for the design and synthesis of novel ice-growth-inhibiting and antifreeze compounds.

Marine Antifreeze Proteins: Structure, Function, and Application to Cryopreservation as a Potential Cryoprotectant

“…Recently, Steven et al claimed the dendrimer-like AFPs showed higher TH values [213], and Phippen et al demonstrated 12 AFP-fused protein cage nanoparticles that increased the TH value to more than 50-fold that of monomeric AFP [214]. A few groups have attempted to synthesize AFP or AFGP derivatives to elucidate the underlying mechanism of action and to develop practical applications [215,216,217,218,219,220,221]. Another interesting approach is the development of cell-internalizable or -penetrating AFPs.…”

Antivirulence Properties of an Antifreeze Protein

“…Antifreeze glycoproteins (AFGPs), a class of AFPs, are characterized by canonical Ala-Ala-Thr or Pro-Ala-Thr repeats with a β-D-galactosyl-(1→3)-α-N-acetyl-D-galactosamine disaccharide attached to each threonine (Carvajal-Rondanelli et al, 2011). Arctic fish AFGPs contain between 4 to 55 repeats, and AFGPs of different length may synergize, suggesting functional differences encoded into the number of tripeptide repeats and spacer sequences between them (Garner and Harding, 2010). …”

Modern Extensions of Native Chemical Ligation for Chemical Protein Synthesis

“…AFGPs are mucin-type glycoprotein natural products isolated from select Arctic and Antarctic fish, where they play a critical role in preventing the growth of ice crystals. Structurally, AFGPs are composed of multiple copies of the repeating tripeptide Ala-Thr-Ala/Pro, in which each Thr residue is α-O-linked to the disaccharide β-D-galactosyl-(1!3)-α-N-acetyl-D-galactosamine (Scheme 18) and range in size from 4 to 50 repeat units [84,85]. In an effort to access large quantities of homogeneous AFGPs for biological studies and applications in materials science, the authors designed a convergent ligation approach to homogeneous AFGPs bearing between 4 and 32 repeat units.…”