@article {2698,
	title = {Barrier Capacity of Hydrophilic Polymer Brushes To Prevent Hydrophobic Interactions: Effect of Graft Density and Hydrophilicity},
	journal = {Macromolecules},
	volume = {42},
	number = {13},
	year = {2009},
	note = {ISI Document Delivery No.: 472NJTimes Cited: 7Cited Reference Count: 57Zou, Yuquan Rossi, Nicholas A. A. Kizhakkedathu, Jayachandran N. Brooks, Donald E.},
	month = {Jul},
	pages = {4817-4828},
	type = {Article},
	abstract = {The performance of biomaterials in contact with biological systems can be greatly affected by hydrophobic interactions at the interface between the biomaterial surface and surrounding biomolecules. Polymer brushes can function as a protective layer, preventing such interfacial hydrophobic interactions. In this paper, a systematic study of the barrier properties of a hydrophilic polymer brush is made by investigating the influence of graft density and its chemical nature (hydrophilicity/hydrophobicity) on hydrophobic interactions with the surface. To achieve this, it series of novel thermoresponsive poly-N-[(2,2-dimethyl-1,3-dioxolane)methyl]acrylamide (PDMDOMA) polymer brushes were grown from silicon wafers via surface-initiated atom transfer radical polymerization. Without changing graft density or degree of polymerization, the hydrophilicity of the PDMDOMA brushes was manipulated by partial or complete hydrolysis or the pendent dioxolane moieties. A lower critical solution temperature (LCST) was observed at 22-24 degrees C, below which the PDMDOMA brush was Found to be in a hydrated state (amphiphilic), while at temperatures above the LCST, the PDMDOMA brush formed a collapsed. more hydrophobic structure. A physical method was developed to analyze the ability of these brushes to act as a barrier against hydrophobic interactions based on AFM force-distance measurements. The adhesive forces between the Si3N4 tip and the silicon wafer surface upon (a) modification with ATRP initiator, (b) grafting of PDMDOMA brushes, and (c) partial and complete hydrolysis of PDMDOMA were investigated. Hydrophobic interactions decreased after each modification, while graft density and the degree of hydrolysis increased the barrier function of the surface layer. In particular, when graft density was above 0.22 chains/nm(2), the barrier capacity completely counteracted the hydrophobic interactions, as evidenced from the disappearance of the adhesive force in AFM measurements. Further Studies revealed that the barrier property its assessed by AFM correlated well with the wettability of the surfaces.},
	keywords = {ATOMIC-FORCE MICROSCOPY, BLOOD-PLASMA, CELL-ADHESION, CHAIN-LENGTH, HUMAN, MOLECULAR-WEIGHT, protein adsorption, SERUM-ALBUMIN, SINGLE-MOLECULE, SURFACE, TRANSFER RADICAL POLYMERIZATION},
	isbn = {0024-9297},
	url = {<Go to ISI>://000268138500067},
	author = {Zou, Y. Q. and Rossi, N. A. A. and Kizhakkedathu, J. N. and Brooks, D. E.}
}
@article {2118,
	title = {Unimolecular Micelles based on Hydrophobically Derivatized Hyperbranched Polyglycerols: Biodistribution Studies},
	journal = {Bioconjugate Chemistry},
	volume = {19},
	number = {11},
	year = {2008},
	note = {ISI Document Delivery No.: 373VOTimes Cited: 7Cited Reference Count: 31Kainthan, Rajesh Kumar Brooks, Donald E.},
	month = {Nov},
	pages = {2231-2238},
	type = {Article},
	abstract = {We recently reported the synthesis and testing of a new class of unimolecular micelles based on hyperbranched polyglycerols as second generation synthetic plasma expanders and as general drug delivery vehicles. A detailed biodistribution study of two derivatized hyperbranched polyglycerols of different molecular weights derivatized with hydrophobic groups and short poly(ethylene glycol) chains is reported in this article. In mice, these materials are nontoxic with circulation half-lives as high as 31 h, controllable by manipulating the molecular weight and the degree of PEG derivatization. Organ accumulation is low, presumably due to the "pegylation" effect. Thermal degradation and hydrolysis data suggest that these polymers are highly stable with a long shelf life, a major advantage for a pharmaceutical product. Degradation under acidic conditions has been observed for these polymers.},
	keywords = {ALBUMIN, BIOLOGICAL EVALUATION, DENDRIMERS, IMMUNOGENICITY, IN-VIVO, LIPOSOMES, MOLECULAR-WEIGHT, POLYETHYLENE-GLYCOL DEGRADATION, POLYMERS, STARCH},
	isbn = {1043-1802},
	url = {<Go to ISI>://000261001800018},
	author = {Kainthan, R. K. and Brooks, D. E.}
}
@article {1428,
	title = {Blood compatibility of novel water soluble hyperbranched polyglycerol-based multivalent cationic polymers and their interaction with DNA},
	journal = {Biomaterials},
	volume = {27},
	number = {31},
	year = {2006},
	note = {ISI Document Delivery No.: 085NOTimes Cited: 48Cited Reference Count: 41Kainthan, Rajesh Kumar Gnanamani, Muthiah Ganguli, Munia Ghosh, Tanay Brooks, Donald E. Maiti, Souvik Kizhakkedathu, Jayachandran N.},
	month = {Nov},
	pages = {5377-5390},
	type = {Article},
	abstract = {A novel class of hyperbranched polymers based on polyglycerol (PG) and poly(ethylene glycol) (PEG) are synthesized by multibranching anionic ring opening polymerization. Multivalent cationic sites are added to these polymers by a post-amination and quarternization reactions. Blood compatibility studies using these polymers at different concentrations showed insignificant effects on complement activation, platelet activation, coagulation, erythrocyte aggregation and hemolysis compared to branched cationic polyethyleneimine (PEI). The degree of quarternization does not have large influence on the blood compatibility of the new polymers. Cytotoxicity of these polymers is significantly lower than that of PEI and is a function of quarternized nitrogen present in the polymer. Also, these polymers bind DNA in the nanomolar range and are able to condense DNA to highly compact, stable, water soluble nanoparticles in the range of 60-80 nm. Gel electrophoresis studies showed that they form electroneutral complexes with DNA around N/P ratio 1 irrespective of the percentage of quarternization under the conditions studied. (c) 2006 Elsevier Ltd. All rights reserved.},
	keywords = {AFM, blood-compatibility, cationic polymers, COAGULATION, COMPLEXES, delivery, DNA, drug, GENE DELIVERY, hyperbranched polymers, IN-VITRO, MOLECULAR-WEIGHT, NANOPARTICLES, OPPOSITELY CHARGED SURFACTANT, PLATELETS, RANDOM COPOLYMER, therapy},
	isbn = {0142-9612},
	url = {<Go to ISI>://000240611000005},
	author = {Kainthan, R. K. and Gnanamani, M. and Ganguli, M. and Ghosh, T. and Brooks, D. E. and Maiti, S. and Kizhakkedathu, J. N.}
}
@article {1225,
	title = {Entropic interaction chromatography: Separating proteins on the basis of size using end-grafted polymer brushes},
	journal = {Biotechnology and Bioengineering},
	volume = {90},
	number = {1},
	year = {2005},
	note = {ISI Document Delivery No.: 909ETTimes Cited: 9Cited Reference Count: 48},
	month = {Apr},
	pages = {1-13},
	type = {Article},
	abstract = {Partitioning of a macromolecule into the interfacial volume occupied by a grafted polymer brush decreases the configurational entropy (Delta S(c)brush) of the terminally attached linear polymer chains due to a loss of free volume. Self-consistent field theory (SCF) calculations are used to show that Delta S(c)brush is a strong function of both the size (MW,) of the partitioning macromolecule and the depth of penetration into the brush volume. We further demonstrate that the strong dependence of Delta S(c)brush on MW, provides a novel and powerful platform, which we call entropic interaction chromatography (EIC), for efficiently separating mixtures of proteins on the basis of size. Two EIC columns, differing primarily in polymer grafting density, were prepared by growing a brush of poly(methoxyethyl acrylamide) chains on the surface of a widepore (1,000-angstrom pores, 64-mu m diameter rigid beads) resin (Toyopearl AF-650M) bearing surface aldehyde groups. Semipreparative 0.1-L columns packed with either EIC resin provide reduced-plate heights of 2 or less for efficient separation of globular protein mixtures over at least three molecular-weight decades. Protein partitioning within these wide-pore EIC columns is shown to be effectively modeled as a thermodynamically controlled process, allowing partition coefficients (K-p) and elution chromatograms to be accurately predicted using a column model that combines SCF calculation of Kp values with an equilibrium-dispersion type model of solute transport through the column. This model is used to explore the dependence of column separation efficiency on brush properties, predicting that optimal separation of proteins over a broad MW, range is achieved at low to moderate grafting densities and intermediate chain lengths. (c) 2005 Wiley Periodicals, Inc.},
	keywords = {ADSORPTION, CHAIN MOLECULES, CONSISTENT-FIELD THEORY, entropic interaction chromatography, equilibrium dispersion, EXCLUSION CHROMATOGRAPHY, GEL FILTRATION, grafted polymer brush, HUMAN SERUM-ALBUMIN, LIQUID-CHROMATOGRAPHY, MODEL, MOLECULAR-WEIGHT, MONTE-CARLO, protein purification, size exclusion chromatography, STATISTICAL-THEORY},
	isbn = {0006-3592},
	url = {<Go to ISI>://000227843800001},
	author = {Pang, P. and Koska, J. and Coad, B. R. and Brooks, D. E. and Haynes, C. A.}
}
@article {4842,
	title = {Hydrogen bonding and catalysis: A novel explanation for how a single amino acid substitution can change the pH optimum of a glycosidase},
	journal = {Journal of Molecular Biology},
	volume = {299},
	number = {1},
	year = {2000},
	note = {ISI Document Delivery No.: 318NCTimes Cited: 96Cited Reference Count: 58},
	month = {May},
	pages = {255-279},
	type = {Article},
	abstract = {The pH optima of family 11 xylanases are well correlated with the nature of the residue adjacent to the acid/base catalyst. In xylanases that function optimally under acidic conditions, this residue is aspartic acid, whereas it is asparagine in those that function under more alkaline conditions. Previous studies of wild-type (WT) Bacillus circulans xylanase (BCX), with an asparagine residue at position 35, demonstrated that its pH-dependent activity follows the ionization states of the nucleophile Glu78 (pK(a) 4.6) and the acid/base catalyst Glu172 (pK(a) 6.7). As predicted from sequence comparisons, substitution of this asparagine residue with an aspartic acid residue (N35D BCX) shifts its pH optimum from 5.7 to 4.6, with an similar to 20 \% increase in activity. The bell-shaped pH-activity profile of this mutant enzyme follows apparent pK(a) values of 3.5 and 5.8. Based on C-13-NMR titrations, the predominant pK(a) values of its active-site carboxyl groups are 3.7 (Asp35), 5.7 (Glu78) and 8.4 (Glu172). Thus, in contrast to the WT enzyme, the pH-activity profile of N35D BCX appears to be set by Asp35 and Glu78. Mutational, kinetic, and structural studies of N35D BCX, both in its native and covalently modified 2-fluoro-xylobiosyl glycosyl-enzyme intermediate states, reveal that the xylanase still follows a double-displacement mechanism with Glu78 serving as the nucleophile. We therefore propose that Asp35 and Glu172 function together as the general acid/base catalyst, and that N35D BCX exhibits a "reverse protonation" mechanism in which it is catalytically active when Asp35, with the lower pK(a), is protonated, while Glu78, with the higher pK(a), is deprotonated. This implies that the mutant enzyme must have an inherent catalytic efficiency at least 100-fold higher than that of the parental WT, because only similar to 1\% of its population is in the correct ionization state for catalysis at its pH optimum. The increased efficiency of N35D BCX, and by inference all "acidic" family 11 xylanases, is attributed to the formation of a short (2.7 Angstrom) hydrogen bond between Asp35 and Glu172, observed in the crystal structure of the glycosyl-enzyme intermediate of this enzyme, that will substantially stabilize the transition state for glycosyl transfer. Such a mechanism may be much more commonly employed than is generally realized, necessitating careful analysis of the pH-dependence of enzymatic catalysis. (C) 2000 Academic Press.},
	keywords = {3-DIMENSIONAL STRUCTURE, 4-BETA-XYLANASES, ACTIVE-SITE, BACILLUS-CIRCULANS XYLANASE, CYCLODEXTRIN GLYCOSYLTRANSFERASE, electrostatics, ENDO-1, GLYCOSYL-ENZYME INTERMEDIATE, ISOTOPE, MOLECULAR-WEIGHT, NMR, NUCLEAR-MAGNETIC-RESONANCE, nucleophile, PANCREATIC ALPHA-AMYLASE, pH-dependent enzyme mechanism, SHIFT, TRICHODERMA-REESEI, X-RAY CRYSTALLOGRAPHY, X-ray structure},
	isbn = {0022-2836},
	url = {<Go to ISI>://000087289400019},
	author = {Joshi, M. D. and Sidhu, G. and Pot, I. and Brayer, G. D. and Withers, S. G. and McIntosh, L. P.}
}
