Phospholipid imprinted polymers as selective endotoxin scavengers

Abstract

Herein we explore phospholipid imprinting as a means to design receptors for complex glycolipids comprising the toxic lipopolysaccharide endotoxin. A series of polymerizable bis-imidazolium and urea hosts were evaluated as cationic and neutral hosts for phosphates and phosphonates, the latter used as mimics of the phospholipid head groups. The bis-imidazolium hosts interacted with the guests in a cooperative manner leading to the presence of tight and well defined 1:2 ternary complexes. Optimized monomer combinations were subsequently used for imprinting of phosphatidic acid as an endotoxin dummy template. Presence of the aforementioned ternary complexes during polymerization resulted in imprinting of lipid dimers – the latter believed to crudely mimic the endotoxin Lipid A motif. The polymers were characterized with respect to template rebinding, binding affinity, capacity and common structural properties, leading to the identification of polymers which were thereafter subjected to an industrially validated endotoxin removal test. Two of the polymers were capable of removing endotoxin down to levels well below the accepted threshold (0.005 EU/mg API) in pharmaceutical production.

Selective Enrichment of Phosphorylated Peptides by Monolithic Polymers Surface Imprinted with bis-Imidazolium Moieties by UV-Initiated Cryopolymerization

“…From the retention and imprinting parameter results presented there, it can be observed that the both the type of imidazolium host functional monomer and the UV radiation source have noticeable influence on the selectivity of the surface imprinted capillary monolithic columns. This is in agreement with our previous reports on imidazolium based receptors for phosphotyrosine 35 and phospholipids 36 . Hence, monocationic host monomers interact more weakly than bis-cationic hosts accounting for the weaker retention and lower IF for IMI1-IMI2 versus IMI3-5.…”

“…The cationic imidazolium (IMI) functional monomers in Figure 1 were synthesized according to published procedures. [35][36][37] Figure 1. Chemical structures of the cationic monomers IMI1-IMI6, the crosslinkers TRIM and PETA, the phosphorylated Fmoc-pS-OEt target used to prepare surface imprinted monoliths selective towards phosphoserine, and the phosphorylated variants of the utilized test probes, Fmoc-pS-OH, Fmoc-pY-OH, and the octapeptides DRVpSIHPF and DRVpYIHPF.…”

Detection of oxytocin, atrial natriuretic peptide, and brain natriuretic peptide using novel imprinted polymers produced with amphiphilic monomers

“…Success of the method had been demonstrated for lysozyme 8 and lipopolysaccharide endotoxin. 9 Amphiphilic monomers have been known to improve interfacial and partitioning properties. 10 Amphiphilic monomers have also been found to facilitate interfacial synthesis to construct MIPs for ovalbumin, lysozyme detection, or mannose-binding proteins.…”

High salt compatible oxyanion receptors by dual ion imprinting

“…phosphopeptides, sulfopeptides, phospholipids, sugar acids, carboxylates. [14][15][16][17]19 Complexation can be easily induced by proton transfer from the acid to bulky amine bases such as pentamethylpiperidine (PMP) or by the use of quaternary ammonium counterions (e.g. tetrabutylammonium, TBA) which moreover have been shown to produce pronounced counterion memory effects.…”

“…Hence potent anion receptors can be prepared by polymerizing host monomers and a crosslinker in presence of the anion guest followed by guest removal. [11][12][13][14][15][16][17][18][19][20][21] The anion preorganizes the host which is covalently xed in a macromolecular scaffold with tunable local polarity. Permanent imprinted sites are achieved post template removal featuring enhanced affinity for the templated ion.…”