ISSN:1075-2617    

DOI:10.1002/psc.2794

年代:2015

数据来源: WILEY

摘要:

The abnormal accumulation of amyloid‐β(Aβ) peptide in the brain is one of the most important hallmarks of Alzheimer's disease. Aβis an aggregation‐prone and toxic polypeptide with 39–43 residues, derived from the amyloid precursor protein proteolysis process. According to the amyloid hypothesis, abnormal accumulation of Aβin the brain is the primary influence driving Alzheimer's disease pathologies. Among all kinds of Aβisoforms, Aβ40 and Aβ42 are believed to be the most important ones. Although these two kinds of Aβdiffer only in two amino acid residues, recent studies show that they differ significantly in their metabolism, physiological functions, toxicities, and aggregation mechanism. In this review, we mainly summarize the similarities and differences between Aβ42 and Aβ40, recent studies on selective inhibitors as well as probes will also be mentioned. Copyright © 2015 European Peptide Society and John

ISSN:1075-2617    

DOI:10.1002/psc.2789

年代:2015

数据来源: WILEY

摘要:

Antimicrobial peptides (AMPs) are considered as potential antibiotic substitutes because of their potent activities. Previous studies mainly focused on the effects of peptide charges and secondary structures, but the self‐assembly of AMPs was neglected. As more and more researchers notice the roles of peptide self‐assembly in AMPs, it has been considered as another important property. In this review, we will discuss the influences of peptide self‐assembly on the activity and mode of action, and some specific features it introduces to the AMPs, such as particular responsiveness, improved cell selectivity and stability and sustained release. In addition, some methods to design self‐assembling AMPs are primarily discussed. With further understanding about the self‐assembling regularity, design of particular self‐assembling AMPs will be very helpful for their applications, especially in the fields of drug delivery and biomedical engineering. Copyright © 2015 European Peptide Society and John Wil

ISSN:1075-2617    

DOI:10.1002/psc.2788

年代:2015

数据来源: WILEY

摘要:

Chemical synthesis or semi‐synthesis of membrane proteins can provide unique molecular tools, such as site‐specific isotope labeling or post‐translationally modified membrane proteins to gain insight into their biophysical and functional characteristics. However, during preparation, purification, and ligation of transmembrane peptides, tremendous challenges are encountered owing to their hydrophobic nature. This review focuses on the recent advances in chemical synthesis strategies of membrane proteins. These strategies help to solubilize the hydrophobic transmembrane peptide sequences under standard purification and chemical ligation conditions to improve their handling properties. Biophysical and functional studies of synthetic membrane proteins are reviewed as well. Copyright © 2014 European Peptide Society and John Wiley&Son

ISSN:1075-2617    

DOI:10.1002/psc.2721

年代:2015

数据来源: WILEY

摘要:

A new cyclopentapeptide dianthin I (1), together with two known ones pseudostellarin A (2) and heterophyllin J (3), was isolated from the aerial parts ofDianthus chinensis. The structure of 1 was elucidated as cyclo‐(Gly1–l–Phe2–l–Pro3–l–Ser4–l–Phe5) on the basis of extensive spectroscopic analyses and chemical methods. Copyright © 2015 European Peptide Society and Jo

ISSN:1075-2617    

DOI:10.1002/psc.2746

年代:2015

数据来源: WILEY

摘要:

Interferon‐alpha (IFNα) is a cytokine that orchestrates innate and adaptive immune responses and potently inhibits proliferation of normal and tumor cells. These properties have warranted the use of IFNα in clinical practice for the treatment of several viral infections and malignancies. However, overexpression of IFNα leads to immunopathology observed in the context of chronic viral infections and autoimmune conditions. Thus, it is desirable to develop therapeutic approaches that aim at suppressing excessive IFNα production. To that end, artificial evolution of peptides from phage display libraries represents a strategy that seeks to disrupt the interaction between IFNα and its cell surface receptor and thus inhibit the ensuing biological effects. Mirror‐image phage display that screens peptide libraries against the D‐enantiomer is particularly attractive because it allows for identification of proteolysis‐resistant D‐peptide inhibitors. This approach, however, relies on the availability of chemically synthesized D‐IFNα composed entirely of D‐amino acids. Here, we describe the synthesis and biological properties of IFNα2b of 165 amino acid residues produced by native chemical ligation, which represents an important first step toward the discovery of D‐peptide antagonists with potential therapeutic applications. Copyright © 2015 European Peptide Society a

ISSN:1075-2617    

DOI:10.1002/psc.2760

年代:2015

数据来源: WILEY

摘要:

A 15‐mer cationicα‐helical antimicrobial peptide HPRP‐A1 was used as the parent peptide to study the effects of peptide secondary structure on the biophysical properties and biological activities. Without changing the amino acid composition of HPRP‐A1, we designed twoα‐helical peptides with either higher or lower helicity compared with the parent peptide, aβ‐sheet peptide and a random coiled peptide usingde novodesign approach. The secondary structures were confirmed by circular dichroism spectroscopy. The threeα‐helical peptides exhibited comparable antibacterial activities, but their hemolytic activity varied from extreme hemolysis to no hemolysis, which is correlated with their helicity. Theβ‐sheet peptide shows poor antibacterial and strong hemolytic activities. More interestingly, the random coil peptide shows no antibacterial activity against Gram‐negative bacteria, weak antibacterial activity against Gram‐positive bacteria, and extremely weak hemolytic activity. Bacterial membrane permeabilization was also testified on peptides with different secondary structures. Tryptophan fluorescence experiment revealed that the peptide binding preference to the lipid vesicles for mimicking the prokaryotic or eukaryotic membranes was consistent with their biological activities. With thede novodesign approach, we proved that it is important to maintain certain contents of amphipathic secondary structure for a desirable biological activity. We believe that thede novodesign approach of relocation of the amino acids within a template sequence could be an effective approach in optimizing the specificity of an antimicrobial peptide. Copyright © 2015 European Peptide Society

ISSN:1075-2617    

DOI:10.1002/psc.2767

年代:2015

数据来源: WILEY

摘要:

To increase the selectivity of chemotherapeutic agents, receptor‐mediated tumor‐targeting approaches have been developed. Here, degarelix [Ac‐D‐Nal‐D‐Cpa‐D‐Pal‐Ser‐Aph(L‐Hor)‐D‐Aph(Cbm)‐Leu‐ILys‐Pro‐D‐Ala‐NH2], a gonadotropin‐releasing hormone antagonist, was employed as a targeting moiety for paclitaxel (PTX). Five PTX–degarelix conjugates were synthesized, in which PTX was attached via disulfide bond to the different position in the degarelix sequence. All of the PTX–degarelix conjugates exhibited a half‐life greater than 10 h determined in human serum. A fluorometric imaging plate reader assay showed that the conjugates LK‐MY‐9 and LK‐MY‐10 had an antagonism efficacy similar to that of degarelix. Thein vitrocytostatic effects of the conjugates were determined by a (3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium) (MTS) assay, and the 50% inhibitory concentration value of the conjugates on 3T3 mouse embryonic fibroblast cells were one order of magnitude higher than the 50% inhibitory concentration values of the conjugates on MCF‐7 human breast cancer cells and HT‐29 human colon cancer cells. Receptor saturation tests further demonstrated that pre‐incubation of the cells with degarelix reduced the efficacy of LK‐MY‐10 in a concentration‐dependent manner. In conclusion, degarelix is a valid and stable moiety that has great potential for targe

ISSN:1075-2617    

DOI:10.1002/psc.2769

年代:2015

数据来源: WILEY

摘要:

Membrane curvature and lipid composition plays a critical role in interchanging of matter and energy in cells. Peptide curvature sensors are known to activate signaling pathways and promote molecular transport across cell membranes. Recently, the 25‐mer MARCKS‐ED peptide, which is derived from the effector domain of the myristoylated alanine‐rich C kinase substrate protein, has been reported to selectively recognize highly curved membrane surfaces. Our previous studies indicated that the naturally occurringl‐MARCKS‐ED peptide could simultaneously detect both phosphatidylserine and curvature. Here, we demonstrate thatd‐MARCKS‐ED, composed by unnaturald‐amino acids, has the same activities as its enantiomer,l‐MARCKS‐ED, as a curvature and lipid sensor. An atomistic molecular dynamics simulation suggests thatd‐MARCKS‐ED may change from linear to a boat conformation upon binding to the membrane. Comparable enhancement of fluorescence intensity was observed betweend‐ andl‐MARCKS‐ED peptides, indicating similar binding affinities. Meanwhile, circular dichroism spectra ofd‐ andl‐MARCKS‐ED are almost symmetrical both in the presence and absence of liposomes. These results suggest similar behavior of artificiald‐ and naturall‐MARCKS‐ED peptides when binding to curved membranes. Our studies may contribute to further understanding of how MARCKS‐ED senses membrane curvature as well as provide a new direction to develop novel membrane curvature probes. Copyright © 2015 Europ

ISSN:1075-2617    

DOI:10.1002/psc.2772

年代:2015

数据来源: WILEY

摘要:

Glycosylation can have a multifaceted impact on the properties and functions of peptides and plays a critical role in interacting with or binding to the target molecules. Herein, based on the previously reported method for macrocyclic glycopeptide synthesis, two series of tyrocidine A glycosylated derivatives (1a–fand2a–f) were synthesized and evaluated for their antibacterial activities to further study the structure and activity relationships (SAR). Biological studies showed that the synthetic glycosylated derivatives had good antibacterial activities towards methicillin‐resistantStaphylococcus aureusand vancomycin‐resistantEnterococcus. SAR studies based on various glycans and linkages were used to enhance the biochemical profile, resulting in the identification of several potent antibiotics, such as1f, with a great improved therapeutic index than tyrocidine A. Copyright © 2015 European Peptide Society and John Wiley&S

ISSN:1075-2617    

DOI:10.1002/psc.2774

年代:2015

数据来源: WILEY