摘要:

The tendency to use the terms homology, similarity, and identity interchangeably persists in comparative biology. When translated to immunology, overlapping the concepts of homology, similarity, and identity complicates the exact definition of the self–nonself dichotomy and, in particular, affects immunopeptidomics, an emerging field aimed at cataloging and distinguishing immunoreactive peptide epitopes from silent nonreactive amino acid sequences. The definition of similar/dissimilar peptides in immunology is discussed with special attention to the analysis of immunological (dis)similarity between two or more protein sequences that equates to measuring sequence similarity with the use of a proper measurement unit such as a length determinant. Copyright © 2012 European Peptide Society and John Wiley&Sons, L

ISSN:1075-2617    

DOI:10.1002/psc.2419

出版商:John Wiley&Sons, Ltd    

年代:2012

数据来源: WILEY

摘要:

The synthetic peptide octarphin (TPLVTLFK) corresponding to the sequence 12–19 of β‐endorphin, a selective agonist of nonopioid β‐endorphin receptor, was labeled with tritium to a specific activity of 29 Ci/mmol. [3H]Octarphin was found to bind to high‐affinity naloxone‐insensitive binding sites on membranes isolated from rat adrenal cortex (Kd = 35.7 ± 2.3 nM,Bmax = 41.0 ± 3.6 pmol/mg protein). The binding specificity study revealed that these binding sites were insensitive not only to naloxone but to α‐endorphin, γ‐endorphin, [Met5]enkephalin, and [Leu5]enkephalin as well. At the same time, the [3H]octarphin‐specific binding with adrenal cortex membranes was inhibited by unlabeled β‐endorphin (Ki = 32.9 ± 3.8 nM). Octarphin at concentrations of 10−9–10−6 M was found to inhibit the adenylate cyclase activity in adrenocortical membranes, whereas intranasal injection of octarphin at doses of 5 and 20 µg/rat was found to reduce the secretion of corticosterone from the adrenals to the bloodstream. Thus, octarphin decreases the adrenal cortex functional activity through the high affinity binding to nonopioid receptor of β‐endorp

ISSN:1075-2617    

DOI:10.1002/psc.2424

出版商:John Wiley&Sons, Ltd    

年代:2012

数据来源: WILEY

摘要:

As part of an ongoing investigation of filamentous fungi for anticancer leads, an active culture was identified from the Mycosynthetix library (MSX 70741, of the order Hypocreales, Ascomycota). The fungal extract exhibited cytotoxic activity against the H460 (human nonsmall cell lung carcinoma) cell line, and bioactivity‐directed fractionation yielded peptaibols 1–12 and harzianums A (13) and B (14). Structure elucidation of 1–12 was facilitated by high‐resolution MS/MS using higher‐energy collisional dissociation and by high field NMR (950 MHz). The absolute configuration was determined by Marfey's analysis of the individual amino acids; the time required for such analysis was decreased via the development of a 10‐min ultra performance liquid chromatography method. The isolated peptaibols (1–12), along with three other peptaibols isolated and elucidated from a different fungus (MSX 57715) of the same order (15–17), were examined for activity in a suite of biological assays, including those for cytotoxic, antibacterial, and anthelmintic activities. Copyright © 2012 European Peptide Society and Jo

ISSN:1075-2617    

DOI:10.1002/psc.2425

出版商:John Wiley&Sons, Ltd    

年代:2012

数据来源: WILEY

摘要:

Three different synthetic strategies were tested to synthesize EGFRvIII peptide (1), which is a functional variant of the epidermal growth factor receptor, a protein that has been well validated as a target for cancer therapy. The initial synthesis was performed with Applied Biosystem (Carlsbad, CA, USA) 433A peptide synthesizer and it indicated that the last three amino acids coupling and Fmoc removal rates were lower than the rest of the sequence. Purity of the crude peptide was 54.5%. The second synthesis was performed manually utilizing C S Bio (Menlo Park, CA, USA) synthesizer and the Kaiser test for reaction monitoring. Because of non‐optimized reaction conditions and an unexpected by‐product, lower purity crude peptide (40.5%) was obtained. Quantitative assays to monitor reactions were developed and demonstrated in gram scale synthesis with C S Bio synthesizer. The optimized synthetic conditions improved the peptide purity to 68.1%. Copyright © 2012 European Peptide Society and John Wiley&S

ISSN:1075-2617    

DOI:10.1002/psc.2428

出版商:John Wiley&Sons, Ltd    

年代:2012

数据来源: WILEY

摘要:

Peptide modifications that improve pharmacological properties are of considerable therapeutic importance. Here we consider the retro (R), inversed (D) and retro‐inversed (RI) isomers of glucagon with respect to structure, stability, toxicity and biological activity. Biologically, RI‐glucagon demonstrated comparablein vivoactivity as L‐glucagon with respect to magnitude and duration of blood sugar elevation following i.p. administration to mice. Structurally, the isomers were investigated through circular dichroism (CD) and nanopore analysis. CD demonstrated a conserved potential for formation of secondary structure, which was independent of the direction of the peptide (L vs R; D vs RI) as well as formation of symmetry‐related structures for the chiral isomers (L vs D; R vs RI). CD, therefore, discriminated chiral but not directional isomers. Nanopore analysis, which depends on interaction of the peptides with chiral pores, discriminated all four isomers on the basis of unique signatures of bumping and translocation. Nanopore analysis offered greater opportunity than CD to discriminate the isomers although neither technique provided a definitive biomarker of biological activity. Functionally, the R and RI isomers resist proteolytic degradation and none of the isomers possess hemolytic activity or cellular toxicity. Collectively, this investigation highlights the potentials and limitations of CD and nanopore analysis for investigation of peptide isomers as well as offering insight into the structural criteria to mimic peptide biological activity. For this example, retro‐inversion, through undefined contributions of increased stability and maintained biological activity, was best suited to mimic the biological activity of the parent peptide. Copyright © 2012 European Peptide Society and John Wiley

ISSN:1075-2617    

DOI:10.1002/psc.2429

年代:2012

数据来源: WILEY

摘要:

There is considerable interest in the sub‐cellular targeting and delivery of biomolecules, therapeutic and imaging agents, and nanoparticles and nanoparticle conjugates into organelles for therapeutic and imaging purposes. To date, a number of studies have used sorting peptides for targeted delivery of cargo into different cell organelles but not into lysosomes. In this study, the delivery of 13‐nm gold nanoparticles across the cell membrane followed by targeted localisation into the lysosomes of a mammalian cell line was examined using novel combinations of cell‐penetrating peptides and lysosomal sorting peptides conjugated to the nanoparticles. Using a combination of fluorescence spectroscopy, fluorescence microscopy and transmission electron microscopy techniques, we show that these nanoconjugates were efficiently and selectively delivered into the lysosomes with minimal cytotoxic effects. This novel targeted delivery system may underpin the development of a new strategy for the treatment of lysosomal storage diseases by exploiting the large surface area of nanoparticles to deliver drugs or replacement enzymes directly to the lysosomes. Copyright © 2012 European Peptide Society and John Wiley&Son

ISSN:1075-2617    

DOI:10.1002/psc.2430

年代:2012

数据来源: WILEY

摘要:

A new series of smaller peptides with tryptophan atC‐terminal and varyingN‐protected amino acids/peptides were designed, synthesized and characterized by analytical and spectroscopic techniques. Analgesic and anti‐inflammatory properties of these peptides were carried outin vivousing tail‐flick method and carrageenan‐induced paw edema method, respectively, at different doses and different time intervals. Most of the peptides synthesized displayed enhanced activity, and particularly tetra and hexapeptides 29–31 were found to be even more potent than the reference standards used. Moreover, some peptides have exhibited promising activity even after 24 h of administration, whereas the reference standards were active only up to 3 h. Further, the compounds did not present any ulcerogenic liability. Copyright © 2012 European Peptide Society and John

ISSN:1075-2617    

DOI:10.1002/psc.2431

年代:2012

数据来源: WILEY