Polysaccharides Peptides And Proteins

Pharmaceutical Monographs, Volume 4: Polysaccharides Peptides and Proteins provides information pertinent to a wide variety of naturally-occurring macromolecules that are either peptide, protein, or polysaccharide in nature, which are important as medicinal and pharmaceutical agents. This monograph presents the basic physical and chemical properties of polysaccharides. Organized into four chapters, this volume begins with an overview of the pharmaceutical importance of the class of compounds known as polysaccharides. This text then provides data on the structure of the polysaccharides that is obtained by isolating and identifying the product formed on hydrolysis of the molecule itself. Other chapters consider plant gums and mucilages as important medicinal and pharmaceutical products. This monograph discusses as well the autohydrolysis of gum arabic. The final chapter deals with the clinical applications of various peptide-type antibiotics. This monograph is a valuable resource for undergraduate students of pharmacy and allied subjects.

Peptide and Protein Drug Delivery Using Polysaccharides offers an interdisciplinary discussion of polysaccharides applied in peptide and protein drug delivery. Chapters consider basic biology of different polysaccharides of current interest and their production at pilot and large-scale stages by various techniques including, but not limited to, cell and hairy root cultures. Other sections examine factors affecting polysaccharide absorption, metabolism, and excretion in nascent, encapsulated, or conjugated forms, with unique coverage of vaccine absorption, metabolism, and drug delivery. A final section considers analytical methods for detection in tissue fluids and homogenates. Accessible figures, tables, and graphical abstracts are included throughout to support understanding. Specific polysaccharides discussed for therapeutic purposes include cellulose, hyaluronic acid, heparin, carageenan, alginic acid, agar and myrrh, acacia, tragacanth, ghatti gum, chitin, chitosan, starch, glycogen and dextran. Adopts an interdisciplinary approach across biochemistry, molecular biology, pharmaceutical sciences and drug delivery, and biotechnological perspectives Features accessible figures, tables and graphical abstracts across all chapters to support understanding Examines various polysaccharides of current interest and aspects affecting their absorption, metabolism, excretion and detection

Sugar chains (glycans) are often attached to proteins and lipids and have multiple roles in the organization and function of all organisms. "Essentials of Glycobiology" describes their biogenesis and function and offers a useful gateway to the understanding of glycans.

Bioinspired matrices assembled on the basis of noncovalent interactions between proteins and polysaccharides have been proved suitable to deliver therapeutically relevant proteins or DNAs. Our initial efforts were dedicated to the relationship between mechanical properties of hydrogels assembled based on specific interactions between low molecular weight heparin (LMWH) and heparin binding peptides (HBPs) such as HIP, ATIII, and PF4 ZIP peptides. The measured differences in affinity and kinetics for LMWH-HBP binding likely lead to observed differences in the phase separation behavior of the poly (ethylene glycol) (PEG)-LMWH/PEG-HIP hydrogels versus the PEG-LMWH/PEG-ATIII hydrogels. More attention has been given to the PF4 ZIP peptide employed for the noncovalent assembly of heparinized hydrogels. Multifunctional star PEG-PF4 ZIP bioconjugates complexed with star PEG-LMWH form hydrogels that exhibit increasing elastic moduli with increasing mole ratio of PEG-PF4 ZIP . The viscoelastic properties of the hydrogels can be controlled via alterations in the ratio between LMWH and PF4 ZIP peptide, and comparisons with other PEG-LMWH/PEG-HBP hydrogels suggest the importance of both LMWH/HBP binding kinetics and the binding capacity of LMWH in determining rheological properties in these hydrogels. Characterization of the PEG-LMWH/PEG-PF4 ZIP hydrogels suggests that useful moduli for soft tissue engineering applications are obtained at physiological temperatures and after applying high shear. Furthermore, in the basic fibroblast growth factor (bFGF) release, bFGF/vascular endothelial growth factor (VEGF) co-release, and hydrogel erosion results, the combination of growth factor (GF) release profiles and hydrogel erosion profiles suggests that GF delivery from the assembled hydrogels is mainly an erosion-controlled process that may permit co-release of GF with PEG-LMWH and may therefore also improve the bioactivity of GF delivered from these matrices. Hydrogels with such engineered mechanical properties and biological activities may find expanded use in controlled delivery of therapeutics and in other biological applications. In addition to the multivalent PEG-HBPs, a growth factor with two LMWH-binding sites, VEGF, was also employed to physically crosslink PEG-unfractionated LMWH based on protein-polysaccharide interactions, and the assembled networks can be selectively eroded in the presence of the growth factor receptors. The VEGF released from these hydrogels is bioactive and able to increase proliferation of VEGF-responsive cell lines. A receptor-mediated hydrogel erosion and protein delivery are suggested from the release of VEGF crosslinks in response to cell surface KDR. Employing similar approaches, other therapeutically important difunctional proteins or synthetic peptides can also act as crosslinks of environmentally-responsive systems and be delivered in a targeted manner. The multivalent PEG-HBPs are also capable of binding both heparin and plasmid DNA sufficiently well to make them valuable for serving as DNA delivery vectors. Transfection studies suggest the PEG-HBPs possess significant transfection efficiency. Apart from the highly toxic PEG-ATIII vector, increased heparin affinity of PEG-HBPs correlated well with increased cellular uptake and increased transfection efficiency. In general, cell surface binding and cellular uptake, mediated by heparan sulfate, play a key role in the transfection pathway. Given that the structures and components of PEG-HBPs can be accurately tuned, the multivalent PEG-HBPs may find broader applications in gene delivery.

Computer-based design and modeling, computational approaches, and instrumental methods for elucidating molecular mechanisms of protein folding and ligand-acceptor interactions are included in Volumes 202 and 203, as are genetic and chemical methods for the production of functional molecules including antibodies and antigens, enzymes, receptors, nucleic acids and polysaccharides, and drugs.

Polymer-Protein Conjugates: From Pegylation and Beyond helps researchers by offering a unique reference and guide into this fascinating area. Sections cover the challenges surrounding the homogeneity of conjugates, their purity and polymer toxicity on long-term use, and how to deal with the risk of immunogenicity. These discussions help researchers design new projects by taking into account the latest innovations for safe and site selective polymer conjugation to proteins. PEG has been the gold standard and likely will play this role for many years, but alternatives are coming into the market, some of which have already been launched. After five decades of improvements, the ideas in this book are entering into a new era of innovation because of the advances in genetic engineering, biochemistry and a better understanding of the results from clinical use of PEG conjugates in humans.