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1. |
Structure–activity study of macropin, a novel antimicrobial peptide from the venom of solitary beeMacropis fulvipes(Hymenoptera: Melittidae) |
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Journal of Peptide Science,
Volume 20,
Issue 6,
2014,
Page 375-384
Lenka Monincová,
Václav Veverka,
Jiřina Slaninová,
Miloš Buděšínský,
Vladimír Fučík,
Lucie Bednárová,
Jakub Straka,
Václav Čeřovský,
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摘要:
A novel antimicrobial peptide, designated macropin (MAC‐1) with sequence Gly‐Phe‐Gly‐Met‐Ala‐Leu‐Lys‐Leu‐Leu‐Lys‐Lys‐Val‐Leu‐NH2, was isolated from the venom of the solitary beeMacropis fulvipes. MAC‐1 exhibited antimicrobial activity against both Gram‐positive and Gram‐negative bacteria, antifungal activity, and moderate hemolytic activity against human red blood cells. A series of macropin analogs were prepared to further evaluate the effect of structural alterations on antimicrobial and hemolytic activities and stability in human serum. The antimicrobial activities of several analogs against pathogenicPseudomonas aeruginosawere significantly increased while their toxicity against human red blood cells was decreased. The activity enhancement is related to the introduction of eitherl‐ ord‐lysine in selected positions. Furthermore, all‐danalog and analogs withd‐amino acid residues introduced at the N‐terminal part of the peptide chain exhibited better serum stability than did natural macropin. Data obtained by CD spectroscopy suggest a propensity of the peptide to adopt an amphipathicα‐helical secondary structure in the presence of trifluoroethanol or membrane‐mimicking sodium dodecyl sulfate. In addition, the study elucidates the structure–activity relationship for the effect ofd‐amino acid substitutions in MAC‐1 using NMR spectroscopy. Copyright ©
ISSN:1075-2617
DOI:10.1002/psc.2625
年代:2014
数据来源: WILEY
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2. |
Characterization and inhibition of AF10‐mediated interaction |
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Journal of Peptide Science,
Volume 20,
Issue 6,
2014,
Page 385-397
Sven Hagen,
Dinah Mattay,
Christina Räuber,
Kristian M. Müller,
Katja M. Arndt,
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摘要:
The non‐random chromosomal translocations t(10;11)(p13;q23) and t(10;11)(p13;q14–21) result in leukemogenic fusion proteins comprising the coiled coil domain of the transcription factor AF10 and the proteins MLL or CALM, respectively, and subsequently cause certain types of acute leukemia. The AF10 coiled‐coil domain, which is crucial for the leukemogenic effect, has been shown to interact with GAS41, a protein previously identified as the product of an amplified gene in glioblastoma. Using sequential synthetic peptides, we mapped the potential AF10/GAS41 interaction site, which was subsequently be used as scaffold for a library targeting the AF10 coiled‐coil domain. Using phage display, we selected a peptide that binds the AF10 coiled‐coil domain with higher affinity than the respective coiled‐coil region of wild‐type GAS41, as demonstrated by phage ELISA, CD, and PCAs. Furthermore, we were able to successfully deploy the inhibitory peptide in a mammalian cell line to lower the expression ofHoxagenes that have been described to be overexpressed in these leukemias. This work dissects molecular determinants mediating AF10‐directed interactions in leukemic fusions comprising the N‐terminal parts of the proteins MLL or CALM and the C‐terminal coiled‐coil domain of AF10. Furthermore, it outlines the first steps in recognizing and blocking the leukemia‐associated AF10 interaction in histiocytic lymphoma cells and therefore, may have significant implications in future diagnostics and therapeutics. Copyright © 2014 European Peptide Society
ISSN:1075-2617
DOI:10.1002/psc.2626
年代:2014
数据来源: WILEY
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3. |
Preparation of truncated orf virus entry fusion complex proteins by chemical synthesis |
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Journal of Peptide Science,
Volume 20,
Issue 6,
2014,
Page 398-405
Ho Yeung,
Paul W. R. Harris,
Christopher J. Squire,
Edward N. Baker,
Margaret A. Brimble,
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摘要:
Members of theChordopoxvirinaesubfamily possess an unusual 11 protein entry–fusion complex (EFC) that is highly conserved and present in all species. The mode of action of this EFC is unknown, and the interactions of the constituent proteins are uncharacterised. Here, we present the chemical synthesis of membrane domain truncated linear constructs of two EFC proteins in orf virus, ORFV036 and 049. By using Boc solid phase peptide synthesis and native chemical ligation methods, these truncated proteins have been readily prepared in milligram quantities. These robust synthetic protocols allow ready access to these polypeptides to facilitate biological studies. Copyright © 2014 European Peptide Society and John Wiley&Sons, L
ISSN:1075-2617
DOI:10.1002/psc.2627
年代:2014
数据来源: WILEY
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4. |
Conformational studies of neurohypophyseal hormones analogues with glycoconjugates by NMR spectroscopy |
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Journal of Peptide Science,
Volume 20,
Issue 6,
2014,
Page 406-414
Emilia A. Lubecka,
Emilia Sikorska,
Alina Marcinkowska,
Jerzy Ciarkowski,
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摘要:
AbstractTwo glycosylated peptides have been studied using NMR spectroscopy supported by molecular modeling. Peptide I is an oxytocin (OT) analogue in which glutamine 4 was replaced by serine with attachedα‐d‐mannose through the oxygenβatom, whereas peptide II is a lysine‐vasopressin (LVP) analogue with lysine 8 side chain modified by the attachment of glucuronic acid through an amide bond. Both peptides exhibit very weak uterotonic effect and are less susceptible to proteolytic degradation than the mother hormones. Additionally, peptide II reveals very weak pressor and antidiuretic activities. Our results have shown that the conformational preferences of glycosylated analogues are highly similar to those of their respective mother hormones. OT glycosylated analogue (I) exhibits a 3,4β‐turn characteristic of OT‐like peptides, and vasopressin‐glycosylated analogue (II) exhibits β‐turns typical of vasopressin‐like peptides. Therefore, the lack of binding of the glycosylated analogues to the receptors can be attributed to a steric interference between the carbohydrate moieties and the receptors. We also consider this to be the reason of the very low activity of the analyzed glycopeptides. We expect that results from these studies will be helpful in designing new OT‐like and vasopressin‐like drugs. Copyright © 2014 European Peptide Societ
ISSN:1075-2617
DOI:10.1002/psc.2628
年代:2014
数据来源: WILEY
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5. |
Potent inhibitors of human matriptase‐1 based on the scaffold of sunflower trypsin inhibitor |
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Journal of Peptide Science,
Volume 20,
Issue 6,
2014,
Page 415-420
Heiko Fittler,
Olga Avrutina,
Martin Empting,
Harald Kolmar,
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摘要:
Sunflower trypsin inhibitor‐1 (SFTI‐1), a bicyclic tetradecapeptide, has become a versatile tool as a scaffold for the development of the inhibitors of therapeutically relevant serine proteases, among them matriptase and kallikreins. Herein, we report the rational design of potent monocyclic and bicyclic inhibitors of human matriptase‐1. We found that the presence of positive charge and lack of bulky residues at the peptideN‐terminus is required for the maintenance of inhibitory activity. Replacement of theN‐terminal glycine residue by lysine allowed for the chemical conjugation with a fluorophor via theε‐amino group without significant loss of inhibitory activity. Head‐to‐tail and side‐chain‐to‐tail cyclization resulted in potent inhibitors with comparable activities against matriptase‐1. The most potent synthetic bicyclic inhibitor found in this study (Ki = 2.6 nM at pH 7.6) is a truncated version of SFTI‐1 (cyclo‐KRCTKSIPPRCH) lacking aC‐terminal proline and aspartate residue. It combines an internal disulfide bond with a peptide macrocycle that is formed through side‐chain‐to‐tail cyclization of theε‐amino group of anN‐terminal lysine and aC‐terminal proline. Copyright © 2014
ISSN:1075-2617
DOI:10.1002/psc.2629
年代:2014
数据来源: WILEY
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6. |
Structure‐activity relationship of Trp‐containing analogs of the antimicrobial peptide gomesin |
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Journal of Peptide Science,
Volume 20,
Issue 6,
2014,
Page 421-428
Tatiana M. Domingues,
Marcus V. Buri,
Sirlei Daffre,
Patricia T. Campana,
Karin A. Riske,
Antonio Miranda,
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摘要:
Gomesin (Gm) has a broad antimicrobial activity making it of great interest for development of drugs. In this study, we analyzed three Gm analogs, [Trp1]‐Gm, [Trp7]‐Gm, and [Trp9]‐Gm, in an attempt to gain insight into the contributions of different regions of the peptide sequence to its activity. The incorporation of the tryptophan residue in different positions has no effect on the antimicrobial and hemolytic activities of the Gm analogs in relation to Gm. Spectroscopic studies (circular dichroism, fluorescence and absorbance) of Gm and its analogs were performed in the presence of SDS, below and above its critical micelle concentration (CMC) (~8 mM), in order to monitor structural changes induced by the interaction with this anionic surfactant (0–15 mM). Interestingly, we found that the analogs interact more strongly with SDS at low concentrations (0.3‐6.0 mM) than close to or above its CMC. This suggests that SDS monomers are able to cover the whole peptide, forming large detergent‐peptide aggregates. On the other hand, the peptides interact differently with SDS micelles, inserting partially into the micelle core. Among the peptides, Trp in position 1 becomes more motionally‐restricted in the presence of SDS, probably because this residue is located at theN‐terminal region, which presents higher conformational freedom to interact stronger with SDS molecules. Trp residues in positions 7 and 9, close to and in the region of the turn of the molecule, respectively, induced a more constrained structure and the compounds cannot insert deeper into the micelle core or be completely buried by SDS monomers. Copyright © 2014 European Peptide Society an
ISSN:1075-2617
DOI:10.1002/psc.2632
年代:2014
数据来源: WILEY
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7. |
Antioxidant properties of a human neuropeptide and its protective effect on free radical‐induced DNA damage |
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Journal of Peptide Science,
Volume 20,
Issue 6,
2014,
Page 429-437
Simin Mohseni,
Shirin Emtenani,
Shamsi Emtenani,
Ahmad Asoodeh,
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摘要:
Human catestatin CgA352–372(SL21) is an endogenous neuropeptide with multiple biological functions. The present study aimed to evaluate the antioxidant, antibacterial, cytotoxic, and DNA damage protective effects of SL21 neuropeptide. SL21 neuropeptide generated from theC‐terminus of chromogranin A (CgA) was synthesized by solid‐phase method. Synthetic peptide was subjected to variousin vitroantioxidant assays including the scavenging of 1,1‐diphenyl‐2‐pycryl‐hydrazyl (DPPH), 2,2‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS·+), and hydroxyl free radicals, metal ion chelation, inhibition of lipid peroxidation, and reducing power. Moreover, protective effect of SL21 on H2O2‐induced DNA damage was analyzed using pTZ57/RT plasmid. Methylthiazoltetrazolium assay was also performed to study the cytotoxic effect of SL21 neuropeptide on human peripheral blood mononuclear cells. Furthermore, antibacterial and hemolysis assays were conducted. The results demonstrated high activities of SL21 in scavenging free radicals (DPPH, ABTS·+, and hydroxyl), chelating of Cu2+/Fe2+metal ions, reducing power, and inhibition of lipid peroxidation in a concentration‐dependent manner. SL21 neuropeptide revealed a protective effect on DNA damage caused by hydroxyl radicals. Interestingly, the peptide exhibited no significant cytotoxicity towards peripheral blood mononuclear cells. Furthermore, SL21 peptide displayed antimicrobial activity againstStaphylococcus aureusandPseudomonas aeruginosawithout any hemolytic activity on human red blood cells. Conclusively, the present study established SL21 (catestatin) as a novel antioxidative peptide that could further be investigated for its potential use as a pharmaceutical agent. Copyright © 2014 European Peptide So
ISSN:1075-2617
DOI:10.1002/psc.2634
年代:2014
数据来源: WILEY
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8. |
Deletion of the carboxyl‐terminal residue disrupts the amino‐terminal folding, self‐association, and thermal stability of an amphipathic antimicrobial peptide |
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Journal of Peptide Science,
Volume 20,
Issue 6,
2014,
Page 438-445
Chang‐Shin Lee,
Wei‐Cheng Tung,
Yu‐Hsin Lin,
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摘要:
Understanding the complex relationship between amino acid sequence and protein behaviors, such as folding and self‐association, is a major goal of protein research. In the present work, we examined the effects of deleting aC‐terminal residue on the intrinsic properties of an amphapathicα‐helix of mastoparan‐B (MP‐B), an antimicrobial peptide with the sequence LKLKSIVSWAKKVL‐NH2. We used circular dichroism and nuclear magnetic resonance to demonstrate that the peptide MP‐B[1‐13]displayed significant unwinding at theN‐terminal helix compared with the parent peptide of MP‐B, as the temperature increased when the residue at position 14 was deleted. Pulsed‐field gradient nuclear magnetic resonance data revealed that MP‐B forms a larger diffusion unit than MP‐B[1‐13]at all experimental temperatures and continuously dissociates as the temperature increases. In contrast, the size of the diffusion unit of MP‐B[1‐13]is almost independent of temperature. These findings suggest that deleting the flexible, hydrophobic amino acid from theC‐terminus of MP‐B is sufficient to change the intrinsic helical thermal stability and self‐association. This effect is most likely because of the modulation of enthalpic interactions and conformational freedom that are specified by this residue. Our results implicate terminal residues in the biological function of an antimicrobial peptide. Copyright © 2014 European P
ISSN:1075-2617
DOI:10.1002/psc.2635
年代:2014
数据来源: WILEY
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9. |
On the limited recognition of inorganic surfaces by short peptides compared with antibodies |
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Journal of Peptide Science,
Volume 20,
Issue 6,
2014,
Page 446-450
Arbel Artzy‐Schnirman,
Enas Abu‐Shah,
Matan Dishon,
Hadas Soifer,
Yotam Sivan,
Yoram Reiter,
Itai Benhar,
Uri Sivan,
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摘要:
The vast potential applications of biomolecules that bind inorganic surfaces led mostly to the isolation of short peptides that target selectively specific materials. The demonstrated differential affinity toward certain surfaces created the impression that the recognition capacity of short peptides may match that of rigid biomolecules. In the following, we challenge this view by comparing the capacity of antibody molecules to discriminate between the (100) and (111A) facets of a gallium arsenide semiconductor crystal with the capacity of short peptides to do the same. Applying selection from several peptide and single chain phage display libraries, we find a number of antibody molecules that bind preferentially a given crystal facet but fail to isolate, in dozens of attempts, a single peptide capable of such recognition. The experiments underscore the importance of rigidity to the recognition of inorganic flat targets and therefore set limitations on potential applications of short peptides in biomimetics. Copyright © 2014 European Peptide Society and John Wiley&Sons, Ltd
ISSN:1075-2617
DOI:10.1002/psc.2636
年代:2014
数据来源: WILEY
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10. |
Issue information |
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Journal of Peptide Science,
Volume 20,
Issue 6,
2014,
Page -
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ISSN:1075-2617
DOI:10.1002/psc.2561
年代:2014
数据来源: WILEY
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