New chemoenzymatic approach to glyco-lipopolymers: practical preparation of functionally active galactose–poly(ethylene glycol)–distearoylphosphatidic acid (Gal–PEG–DSPA) conjugate

Polymerization of Ethylene Oxide, Propylene Oxide, and Other Alkylene Oxides: Synthesis, Novel Polymer Architectures, and Bioconjugation

“…PEGylation is very often associated with modification of proteins and peptides, but a large variety of molecules and surfaces have been PEGylated. This includes lipids (for the preparation of stealth liposomes, − i.e., mPEG–1,2-distearoyl- sn -glycero-3-phosphoethanolamine (DSPE), folate–PEG–DSPE, the disulfide-linked cleavable lipopolymer, mPEG–dithiodipropionate (DTP)–DSPE, and Gal-PEG-DSPA), DNA, and oligonucleotides (PEGylated nucleotides show improved solubility, inferior degradation through nucleases, as well as cell membrane permeability − ), nanoparticles, , affinity ligands (PEGylated affinity ligands are often used for purification of biopharmaceuticals , ), cofactors (used in biotechnological processes , ), and drugs. The PEGylation of drugs disparate to proteins and peptides provides enhanced water-solubility, higher stability to pH and temperature changes, which translates to better shelf half-life.…”

2 Synthetic methods : Part (v) Enzyme methods

“…A β-galactosidase has been used to glycosylate the hydroxyl terminus of benzylPEG (MW 2000). 181 Regioselective β(1,4)-galactosylation of GlcNAcα(1,2)ManαSPh using a galactosidase from Bifidobacterium bifidium proved a key step in the first synthesis of the serine tetrapeptide from α-dystroglycan, which contains a rare Man-Ser linkage. 182 Chemical glycosylation of the serine side chain through NIS, TfOH activation of a protected form of the thioglycoside that is the product of galactosylation followed by sialyltransferase mediated sialylation gave the final product in just 9 steps.…”

Preparative biotransformations

“…One example of enzyme-catalysed formation of a phosphate ester is the coupling of the C 6 -OH silyl derivative of β-Gal-O-PEG-OH and distearoyl phosphatidylcholine which was accomplished in 50% yield using phospholipase-D in CCl 4acetate buffer (pH 5.6) to give, after desilylation, the galactose derivative 73. 145…”