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Enoxaparin, one of the most important low-molecular-weight heparins (LMWHs), is widely used as a clinical anticoagulant. Different production processes and animal sources of its precursor (unfractionated heparin) can result in the structural diversity of enoxaparin. In this study, 38 lots of enoxaparin prepared at different times, from different providers and animal sources, were systematically analyzed. SEC and SAX were used to analyze the oligosaccharide dispersity and structural compositions (disaccharide domains) of enoxaparins by size and charge, respectively. The results provide clues as to whether the structural variations in enoxaparin, observed in oligosaccharide mapping and/or disaccharide analysis, are attributable to differences in the animal sources of its heparin precursor or enoxaparin production processes based on times or brands. The representative enoxaparins were fingerprinted with online multiple heart-cut two-dimensional liquid chromatography-mass spectrometry (MHC-2DLC-MS). The profiles in MHC-2DLC-MS showed the detailed structural information of enoxaparins. In addition, the binding capacities to antithrombin III (AT) of these 38 lots of enoxaparins were detected using surface plasmon resonance (SPR) with the competitive inhibition mode. The results showed that the glycan size distribution of an enoxaparin is more related to its production process. The disaccharide composition, sequence and the variety of glycans of an enoxaparin are more related to its AT binding-based anticoagulant activity. [ABSTRACT FROM AUTHOR]

We utilize the supramolecular self-assembling peptide of Nap-GDFDFDYDK to construct chemically programmed, self-assembling and self-adjuvant MUC1-based antitumor vaccines. The vaccines, with antigen and adjuvant conjugation through covalent bonds, elicited both humoral and cellular immune responses. [ABSTRACT FROM AUTHOR]

We have designed and synthesized MUC1-fibroblast stimulating lipopeptide 1 conjugates as potential self-adjuvanting cancer vaccines using a linear solid phase peptide synthesis strategy. These vaccine candidates have elicited T cell dependent immune response and the induced antibodies showed intense specific binding affinity to human MCF-7 cells. [ABSTRACT FROM AUTHOR]

Addition polymerization usually results in polymers with long carbon–carbon main chains. Cyanoacrylate (CA) is arguably an important example of such polymerization and has gained widespread acceptance as an all-purpose adhesive. However, CA-based medical adhesives have never been approved by the U.S. Federal Drug Administration for use below the skin, mainly due to the low biodegradability and biocompatibility of their solid glue after polymerization. In this research, a cross-linking strategy involving the combination of alkyl-CA and the cross-linking agent poly(ethylene glycol)–di(cyanoacrylate) (CA–PEG–CA) to form a copolymeric network was used to synthesize a new generation of biodegradable CA medical adhesives. The degradability could be modulated by adjusting the ratio of CA–PEG–CA to alkyl-CA and the length of PEG. An optimal composite adhesive, LKJ11, was shown to have excellent biodegradability, adhesive capability, and biocompatibility. Importantly, the molecular weight of polycyanoacrylate chains in the polymerized LKJ11 was greatly reduced compared to those polymerized from pure butyl-CA. Thus, the degradation product could be readily extracted. The results showed that LKJ11 represents a new generation of CA-based biodegradable medical adhesives. This advance also provides a general strategy to facilitate the conversion of other polymers with long carbon–carbon main chains to a biodegradable form, thereby expanding the novel applications available for traditional polymeric materials. [ABSTRACT FROM AUTHOR]

Micelles with surface morpholino groups were stealthy at blood and normal tissue pH (7.4) due to the unprotonated hydrophilic morpholino groups on the surfaces. At tumor pH (＜7), the micelle surfaces were positively charged because of the protonation of the morpholino groups, which promoted the cellular uptake of the micelles. [ABSTRACT FROM AUTHOR]

Heparin is unique as one of the oldest drugs currently still in widespread clinical use as an anticoagulant, a natural product, one of the first biopolymeric drugs, and one of the few carbohydrate drugs. Recently, certain batches of heparin have been associated with anaphylactoid-type reactions, some leading to hypotension and death. These reactions were traced to contamination with a semi-synthetic oversulfated chondroitin sulfate (OSCS). This Highlight reviews the heparin contamination crisis, its resolution, and the lessons learned. Pharmaceutical scientists now must consider dozens of natural and synthetic heparinoids as potential heparin contaminants. Effective assays, which can detect both known and unknown contaminants, are required to monitor the quality of heparin. Safer and better-regulated processes are needed for heparin production.