1,721,312 research outputs found
Early Career Nurses' Need Fulfillment Profiles: A Longitudinal Person-Centered Perspective on their Nature, Stability, Determinants and Consequences
No full textSupplemental materials for Dr. Istvan Toth-Kiraly's "Early Career Nurses' Need Fulfillment Profiles: A Longitudinal Person-Centered Perspective on their Nature, Stability, Determinants and Consequences
Early Career Nurses' Need Fulfillment Profiles: A Longitudinal Person-Centered Perspective on their Nature, Stability, Determinants and Consequences
No full textSupplemental materials for Dr. Istvan Toth-Kiraly's "Early Career Nurses' Need Fulfillment Profiles: A Longitudinal Person-Centered Perspective on their Nature, Stability, Determinants and Consequences
The influence of incorporating lipids or liposaccharides on the particle size of peptide therapeutics
No full textOral absorption enhancement of dipeptide L-Glu-L-Trp-OH by lipid and glycosyl conjugation
No full textIn recent years, the conjugation of sugar moieties and lipoamino acids has been extensively investigated as a mean to enhance the stability towards enzymatic degradation and the permeability across biological membranes of poorly orally available drugs, including peptides. In this prospect, a library of novel derivatives of the dipeptide L-Glu-L-Trp, a naturally occurring thymic immunomodulator with high hydrophilic character and low membrane permeability, was designed and synthesised by conjugating 2-amino-dodecanoic acid (C12) and/or 1-amino--D-glucuronic acid (GlcAN), -D-glucuronic acid (GlcA) and N--D-glucopyranosylamine succinamic acid (GlsNS) residues to the Glu-Trp scaffold, using an Fmoc solid-phase peptide synthesis strategy on trichlorotrityl resin. A cellobiose derivative was also prepared in solution. The synthesized peptides showed no sign of toxicity to red blood cells at 200 M (haemolysis assay) and their resistance against enzymatic hydrolysis, assessed in Caco-2 homogenates, was usually significantly increased, particularly for the C-terminal conjugates. Several derivatives also saw their apparent permeability values greatly enhanced and one of the conjugates tested proved to be able to release the initial dipeptide after penetrating Caco-2 monolayers. An initial in vivo experiment was then carried out in male Wistar rats to examine the effect of conjugation on the absorption rate and bioavailability. © 2008 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 90: 633-643, 2008
Synthesis and in vivo studies of carbohydrate-based vaccines against group A Streptococcus
No full textCarbohydrates, as carriers, providing numerous attachment points for the conjugation of peptide antigens and their optimal orientation for the recognition by cells of the immune system, reducing degradation of the attached peptide antigens and many other advantages make carbohydrate-based vaccine highly promising approach. Multiple copies of a single group A streptococcal (GAS) M protein derived specific peptide antigens (J8 or J14) were coupled onto carbohydrate cores (D-glucose and D-galactose) linked to lipophilic amino acids to produce a self-adjuvanting liposaccharide vaccine against GAS strains. In vivo experiments showed high serum IgG antibody titers against each of the incorporated peptide epitopes, J8 or J14
Functional polymeric nano/microparticles for protein and DNA vaccine delivery.
No full textThe use of particulate polymeric carriers holds great promise for the development of effective and affordable DNA and protein subunit vaccines. Rational development of such vaccine formulations requires a detailed understanding of their physico-chemical properties, cell-free and in vitro behaviour, in addition to particle uptake and processing mechanisms to antigen presenting cells capable of stimulating safe and effective immune responses. We here provide an overview on functional polymeric nano- and micro-particles designed for surface adsorption of proteins and DNA antigens currently under investigation for the formulation of new vaccines, including comments on their preparation method, antigen delivery strategy, cell-free and in vitro behaviour. In addition, we focus on their influence in activating antigen-specific humoral and/or cellular immune responses and on their potential for the development of new vaccines
Development of conformational mimetics of conserved Streptococcus pyogenes minimal epitope as vaccine candidates
No full textOne of the factors responsible for the poor immunogenicity of synthetic peptide antigens is the lack of conformational integrity. Embedding the minimal epitopes in helix-promoting peptide sequences has successfully enhanced the immunogenicity of the epitopes derived from the α-helical regions of the M protein of group A streptococci (Streptococcus pyogenes, GAS). However, the introduction of "foreign" peptide sequences is believed to have an unfavourable impact on the antigen specificity. In the current study, we employed a non-peptide approach, using topological carbohydrate templates, to induce helical conformation of the peptide antigens. Utilized together with the advances of the lipid core peptide system and chemoselective ligation, five GAS vaccine candidates incorporating the minimal epitope J14i (ASREAKKQVEKALE) were synthesized with high purity. Circular dichroism studies indicated that the template-assembled peptides formed -helix bundles. This atom-economic strategy also reduces the complexity and cost of vaccine production by simply reducing the peptide epitope size
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