Effects of Saccharide Spacing and Chain Extension on Toxin Inhibition by Glycopolypeptides of Well-Defined Architecture

Polizzotti, Brian D.; Maheshwari, Ronak; Vinkenborg, Jan L.; Kiick, Kristi L.

doi:10.1021/ma070725o

Cited by 66 publications

(95 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To study effect of saccharide spacing on multivalent binding (Polizzotti, et al, 2007) TOF (DHB) Lactose-substituted polystyrene By nitroxide-mediated radical polymerization of styrene carrying acetylated lactose (Miura, et al, 2007a) Methacrylamide-carbohydrate polymers (Tsuji, et al, 2007) TOF Sialic acid-containing polymers For use in attenuation of β-amyloid peptide in Alzheimer's disease (Cowan, et al, 2008) Vinyl polymers with laterally attached 4,4′′-digalactosyloxyp-terphenyl side groups Synthesis and chiroptical properties TOF (Cui, et al, 2008b) …”

Section: Maldi Osw Saponinsmentioning

confidence: 99%

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2007–2008

Harvey

2011

Mass Spectrometry Reviews

View full text Add to dashboard Cite

This review is the fifth update of the original review, published in 1999, on the application of MALDI mass spectrometry to the analysis of carbohydrates and glycoconjugates and brings coverage of the literature to the end of 2008. The first section of the review covers fundamental studies, fragmentation of carbohydrate ions, use of derivatives and new software developments for analysis of carbohydrate spectra. Among newer areas of method development are glycan arrays, MALDI imaging and the use of ion mobility spectrometry. The second section of the review discusses applications of MALDI MS to the analysis of different types of carbohydrate. Specific compound classes that are covered include carbohydrate polymers from plants, N- and O-linked glycans from glycoproteins, biopharmaceuticals, glycated proteins, glycolipids, glycosides and various other natural products. There is a short section on the use of MALDI mass spectrometry for the study of enzymes involved in glycan processing and a section on the use of MALDI MS to monitor products of the chemical synthesis of carbohydrates with emphasis on carbohydrate-protein complexes and glycodendrimers. Corresponding analyses by electrospray ionization now appear to outnumber those performed by MALDI and the amount of literature makes a comprehensive review on this technique impractical. However, most of the work relating to sample preparation and glycan synthesis is equally relevant to electrospray and, consequently, those proposing analyses by electrospray should also find material in this review of interest.

show abstract

Section: Maldi Osw Saponinsmentioning

confidence: 99%

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2007–2008

Harvey

2011

Mass Spectrometry Reviews

View full text Add to dashboard Cite

show abstract

“…

…”

mentioning

confidence: 99%

Stable and Potent Polyvalent Anthrax Toxin Inhibitors: Raft‐Inspired Domain Formation in Liposomes that Contain PEGylated Lipids

Rai¹,

Vance²,

Poon³

et al. 2008

Chemistry A European J

View full text Add to dashboard Cite

The design of polyvalent molecules [1][2][3][4][5], consisting of multiple copies of a ligand attached to a suitable scaffold, represents a promising approach for designing potent inhibitors of pathogens and microbial toxins [1,[6][7][8][9][10][11]. Liposomes are particularly attractive scaffolds for designing polyvalent inhibitors [9,10,[12][13][14][15]; however, the poor colloidal stability of conventional liposomes and their short circulation times in vivo [16,17] are major obstacles limiting their therapeutic use. We describe the design of highly stable and active polyvalent anthrax toxin inhibitors based on liposomes incorporating polyethylene glycol (PEG)-functionalized lipids (PEGylated liposomes). Furthermore, drawing from the concept of lipid rafts [15,18,19] -domains that are believed to exist in cellular membranes -we have designed heterogeneous domain-containing PEGylated liposomes that are considerably more active than their homogeneous counterparts (Scheme 1). These raft-mimetic PEGylated polyvalent liposomes are attractive not only for designing inhibitors for toxins and pathogens, but also for the design of efficient targeted drug delivery systems.While liposomes have been investigated extensively for applications in drug delivery, as described above, conventional liposomes are limited in effectiveness because of their low colloidal stability and their rapid uptake by macrophage cells of the immune system, predominantly in the liver and spleen [20]. The ability to enhance the physical stability and extend the circulation lifetime through modification with PEG, achieved by using lipids with PEG attached to their hydrophilic head groups, has proven to be useful in the context of drug delivery [17,[20][21][22]. We first tested whether the use of PEGylated liposomes (Scheme 1b) would enable the design of stable and active polyvalent anthrax lethal toxin (LeTx) inhibitors.To that end, we made liposomes (100 nm diameter) composed of a 19:1 mixture of 1,2-Distearoyl-sn-Glycero-3-Phosphocholine (DSPC) and a pyridyl dithiopropionate derivative of L-α-Distearoyl Phosphatidylethanolamine-N-[Amino(Polyethylene Glycol)2000] (DSPE-PEG2000-PDP). We functionalized these liposomes with an inhibitory peptide HTSTYWWLDGAPC [9,23] (4.7%) that binds to the heptameric cell-binding component of anthrax toxin, [PA 63 ] 7 , thereby blocking the binding of the toxic enzyme lethal factor (LF). Inhibition of the binding of LF to [PA 63 ] 7 prevents the cytosolic delivery of LF, thereby inhibiting cell death. Peptide-functionalized PEGylated liposomes protected RAW264.7 cells from LeTx with a half maximal inhibitory concentration (IC 50 ) of about 35 nM on a per-peptide basis; control PEGylated liposomes functionalized with thioglycerol showed no inhibitory activity (Fig. 1a). Furthermore, as seen in Fig. 1a, the activity of the polyvalent PEGylated liposomes (Scheme 1b) was comparable to that of conventional (non-PEGylated) DSPC-based liposomes (Scheme 1a) with the same peptide density (20 nM), indicating that the use of ...

show abstract

“…[13] Several groups have designed potent polyvalent inhibitors of other toxins such as the heat-labile enterotoxin (LT) from E. coli, the Shigalike toxin (Stx) from enterohemorrhagic E. coli (EHEC) strain O157:H7 and the cholera toxin. [1,[19][20][21][22][23][24][25] Guided by the crystal structure of the Shigalike toxin I (Stx-I) from E. coli in complex with an analogue of its carbohydrate receptor, Kitov and co-workers designed oligovalent inhibitors consisting of receptor analogues tethered to a glucose molecule as the central core. The inhibitor, termed as "Starfish" (Figure 2), protected Vero cells against both Stx-I and II.…”

Section: Design Of Polyvalent Inhibitors Of Toxins and Virusesmentioning

confidence: 99%

The Design of Polyvalent Therapeutics

Joshi

Vance

Rai

et al. 2008

Chemistry A European J

View full text Add to dashboard Cite

show abstract

Effects of Saccharide Spacing and Chain Extension on Toxin Inhibition by Glycopolypeptides of Well-Defined Architecture

Cited by 66 publications

References 69 publications

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2007–2008

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2007–2008

Stable and Potent Polyvalent Anthrax Toxin Inhibitors: Raft‐Inspired Domain Formation in Liposomes that Contain PEGylated Lipids

The Design of Polyvalent Therapeutics

Contact Info

Product

Resources

About