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1. |
I‐conotoxin superfamily revisited |
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Journal of Peptide Science,
Volume 12,
Issue 11,
2006,
Page 679-685
Sukanta Mondal,
Rajasekaran Mohan Babu,
Rajasekaran Bhavna,
Suryanarayanarao Ramakumar,
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摘要:
AbstractThe I‐conotoxin superfamily (I‐Ctx) is known to have four disulfide bonds with the cysteine arrangement C‐C‐CC‐CC‐C‐C, and the members inhibit or modify ion channels of nerve cells. Recently, Olivera and co‐workers (FEBS J. 2005; 272: 4178–4188) have suggested that the previously described I‐Ctx should now be divided into two different gene superfamilies, namely, I1and I2, in view of their having two different types of signal peptides and exhibiting distinct functions. We have revisited the 28 entries presently grouped as I‐Ctx in UniProt Swiss‐Prot knowledgebase, and on the basis ofin silicoanalysis have divided them into I1and I2superfamilies. The sequence analysis has provided a framework forin silicoannotation enabling us to carry out computer‐based functional characterization of the UniProtKB/TrEMBL entry Q59AA4 fromConus milesand to predict it as a member of the I2superfamily. Furthermore, we have predicted the mature toxin of this entry and have proposed that it may be an inhibitor of voltage‐gated potassium channels. Copyright © 2006 European Peptide Soci
ISSN:1075-2617
DOI:10.1002/psc.778
出版商:John Wiley&Sons, Ltd.
年代:2006
数据来源: WILEY
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2. |
Solid‐phase synthesis ofC‐terminally modified peptides |
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Journal of Peptide Science,
Volume 12,
Issue 11,
2006,
Page 686-692
Hefziba T. Ten Brink,
Joris T. Meijer,
Remon V. Geel,
Mark Damen,
Dennis W. P. M. Löwik,
Jan C. M. van Hest,
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摘要:
AbstractIn this paper, a straightforward and generic protocol is presented to label theC‐terminus of a peptide with any desired moiety that is functionalized with a primary amine. Amine‐functional molecules included are polymers (useful for hybrid polymers), long alkyl chains (used in peptide amphiphiles and stabilization of peptides), propargyl amine and azido propyl‐amine (desirable for ‘click’ chemistry), dansyl amine (fluorescent labeling of peptides) and crown ethers (peptide switches/hybrids). In the first part of the procedure, the primary amine is attached to an aldehyde‐functional resin via reductive amination. To the secondary amine that is produced, an amino acid sequence is coupled via a standard solid‐phase peptide synthesis protocol. Since one procedure can be applied for any given amine‐functional moiety, a robust method forC‐terminal peptide labeling is obtained. Copyright © 2006 European Peptide Society and Jo
ISSN:1075-2617
DOI:10.1002/psc.780
出版商:John Wiley&Sons, Ltd.
年代:2006
数据来源: WILEY
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3. |
Novel α‐conotoxins identified by gene sequencing from cone snails native to Hainan, and their sequence diversity |
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Journal of Peptide Science,
Volume 12,
Issue 11,
2006,
Page 693-704
Sulan Luo,
Dongting Zhangsun,
Ben Zhang,
Yaru Quan,
Yong Wu,
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摘要:
AbstractConotoxins (CTX) from the venom of marine cone snails (genusConus) represent large families of proteins, which show a similar precursor organization with surprisingly conserved signal sequence of the precursor peptides, but highly diverse pharmacological activities. By using the conserved sequences found within the genes that encode the α‐conotoxin precursors, a technique based on RT‐PCR was used to identify, respectively, two novel peptides (LiC22, LeD2) from the two worm‐huntingConusspeciesConus lividus,andConus litteratus, and one novel peptide (TeA21) from the snail‐huntingConusspeciesConus textile, all native to Hainan in China. The three peptides share an α4/7 subfamily α‐conotoxins common cysteine pattern (CCX4CX7C, two disulfide bonds), which are competitive antagonists of nicotinic acetylcholine receptor (nAChRs). The cDNA of LiC22N encodes a precursor of 40 residues, including a propeptide of 19 residues and a mature peptide of 21 residues. The cDNA of LeD2N encodes a precursor of 41 residues, including a propeptide of 21 residues and a mature peptide of 16 residues with three additional Gly residues. The cDNA of TeA21N encodes a precursor of 38 residues, including a propeptide of 20 residues and a mature peptide of 17 residues with an additional residue Gly. The additional residue Gly of LeD2N and TeA21N is a prerequisite for the amidation of the precedingC‐terminal Cys. All three sequences are processed at the common signal site ‐X‐Arg‐ immediately before the mature peptide sequences. The properties of the α4/7 conotoxins known so far were discussed in detail. Phylogenetic analysis of the new conotoxins in the present study and the published homologue of α4/7 conotoxins from the otherConusspecies were performed systematically. Patterns of sequence divergence for the three regions of signal, proregion, and mature peptides, both nucleotide acids and residue substitutions in DNA and peptide levels, as well as Cys codon usage were analyzed, which suggest how these separate branches originated. Percent identities of the DNA and amino acid sequences of the signal region exhibited high conservation, whereas the sequences of the mature peptides ranged from almost identical to highly divergent between inter‐ and intra‐species. Notably, the diversity of the proregion was also high, with an intermediate percentage of divergence between that observed in the signal and in the toxin regions. The data presented are new and are of importance, and should attract the interest of researchers in this field. The elucidated cDNAs of these toxins will facilitate a better understanding of the relationship of their structure and function, as well as the process of their evolutionary relationships. Copyright © 2006 European Peptide Socie
ISSN:1075-2617
DOI:10.1002/psc.781
出版商:John Wiley&Sons, Ltd.
年代:2006
数据来源: WILEY
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4. |
Cyclic insulin‐regulated aminopeptidase (IRAP)/AT4receptor ligands |
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Journal of Peptide Science,
Volume 12,
Issue 11,
2006,
Page 705-713
Andreas Axén,
Gunnar Lindeberg,
Heidi Demaegdt,
Georges Vauquelin,
Anders Karlén,
Mathias Hallberg,
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摘要:
AbstractThe angiotensin IV receptor (AT4receptor) is the insulin‐regulated aminopeptidase enzyme (IRAP, EC 3.4.11.3). This membrane‐spanning enzyme belongs to the M1 family of zinc‐dependent metallo‐peptidases. It has been proposed that AT4receptor ligands exert their physiological effects by binding to the active site of IRAP and thereby inhibiting the catalytic activity of the enzyme. The biological activity of a large series of linear angiotensin IV analogs was previously disclosed. Herein, the synthesis and biological evaluation of a series of angiotensin IV analogs, encompassing macrocyclic ring systems of different sizes, are presented. It is demonstrated that disulfide cyclizations of angiotensin IV can deliver ligands with high IRAP/AT4receptor affinity. One ligand, with an 11‐membered ring system (4), inhibited human IRAP and aminopeptidase N (AP‐N) activity with similar potency as angiotensin IV but was considerably more stable than angiotensin IV toward enzymatic degradation. The compound provides a promising starting point for further optimization toward more drug‐like derivatives. The cyclic constrained analogs allowed us to propose a tentative bioactive conformation of angiotensin IV and it seems that the peptide adopts an inverse γ‐turn at theC‐terminal. Copyright © 2006 European Peptide Society and J
ISSN:1075-2617
DOI:10.1002/psc.782
出版商:John Wiley&Sons, Ltd.
年代:2006
数据来源: WILEY
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5. |
Is lGnRH‐III the most potent GnRH analog containing only natural amino acids that specifically inhibits the growth of human breast cancer cells? |
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Journal of Peptide Science,
Volume 12,
Issue 11,
2006,
Page 714-720
Krisztina Herédi‐Szabó,
Richard F. Murphy,
Sándor Lovas,
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摘要:
AbstractAnalogs of the decapeptide, gonadotropin‐releasing hormone (GnRH), used in the treatment of hormone‐dependent tumors, contain numerous unnatural amino acids, giving rise to many adverse effects. lGnRH‐III, a natural isoform of GnRH isolated from the sea lamprey, is a weak agonist of GnRH in the pituitary, but inhibits the growth of human cancer cells in micromolar concentrations. As lGnRH‐III is not a natural ligand in humans, it is possible that a more potent peptide, also containing only natural amino acids, can be synthesized. A positional scanning peptide library, focused on the variable region of the GnRH family of peptides, residues 5–8, was synthesized. The synthesized peptides were analyzed in competitive binding experiments and six new analogs were designed on the basis of the results. Their biological activities were evaluated in cell growth experiments. The only natural sequence selected was chicken GnRH‐II. The synthetic library did not yield a more potent peptide than lGnRH‐III. Copyright © 2006 European Peptide Society and John W
ISSN:1075-2617
DOI:10.1002/psc.783
出版商:John Wiley&Sons, Ltd.
年代:2006
数据来源: WILEY
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6. |
Purification and characterization of the central segment of prothymosin‐α: methodology for handling highly acidic peptides |
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Journal of Peptide Science,
Volume 12,
Issue 11,
2006,
Page 721-725
Christopher L. Wilson,
William B. Monteith,
Allison S. Danell,
Colin S. Burns,
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摘要:
AbstractProthymosin‐α is a highly acidic protein consisting of 110 amino acids. The central segment of this protein, residues 51–89, is thought to be involved in metal binding which may be necessary for its physiological function. To carry out studies of this peptide, this central segment was synthesized in a linear fashion using Fmoc‐based methods on rink amide MBHA resin. However, this peptide could not be purified with the typical straightforward approach of RP HPLC followed by negative mode electrospray ionization mass spectrometry (ESI‐MS). This was attributed to the high proportion of acidic residues: 26 out of the 39 residues are aspartic and glutamic acids. The acidity of the peptide prevented retention on the RP HPLC column. Additionally, the ability of the highly negatively charged peptide to retain sodium ions prevented molecular weight determination with ESI‐MS. A systematic approach to the purification of this highly acidic peptide was undertaken. Ultimately, strong anion exchange chromatography was used to purify the peptide. Extensive desalting using dialysis was required prior to ESI‐MS, and the choice of the buffer proved to be critical. In the end, a purification method was devised that yielded a highly purified peptide and is readily compatible with analysis by ESI‐MS. Copyright © 2006 European Peptide Society and John
ISSN:1075-2617
DOI:10.1002/psc.784
出版商:John Wiley&Sons, Ltd.
年代:2006
数据来源: WILEY
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7. |
Analysis of novel angiotensin‐I‐converting enzyme inhibitory peptides from protease‐hydrolyzed marine shrimpAcetes chinensis |
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Journal of Peptide Science,
Volume 12,
Issue 11,
2006,
Page 726-733
HE Hai‐Lun,
Chen Xiu‐Lan,
Sun Cai‐Yun,
Zhang Yu‐Zhong,
Zhou Bai‐Cheng,
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摘要:
AbstractAcetes chinensisis an underutilized shrimp species thriving in the Bo Hai Gulf of China. In a previous study, we had used the protease fromBacillussp. SM98011 to digest this kind of shrimp and found that the oligopeptide‐enriched hydrolysate possessed antioxidant activity and high angiotensin I‐converting enzyme (ACE) inhibitory activity with an IC50value of 0.97 mg/ml. In this paper, by ultrafiltration, gel permeation chromatography and reversed‐phase high‐performance liquid chromatography (RP‐HPLC), five peptides with high ACE inhibitory activity were purified from the shrimp hydrolysates and their sequences were identified by amino acid composition analysis and molecular weight (MW) analysis. Three of them, FCVLRP (a), IFVPAF (f) and KPPETV (j), were novel ACE inhibitory peptides. Their IC50values were 12.3 µM, 3.4 µMand 24.1 µM, respectively, and their recoveries were 30 mg/100 g (solid basis of shrimp), 19 mg/100 g and 33 mg/100 g, respectively. Lineweaver‐Burk plots for the three novel peptides showed that they are all competitive inhibitors. To test the ACE inhibitory activity of peptide a, f, j after they were digested by digestive enzymesin vivo, 12 derived peptides from FCVLRP and IFVPAF were synthesized based on their amino acid sequences and the cleavage sites of digestive enzymes. No digestive enzyme cleavage site was found in KPPETV. The IC50values of the derived peptides were determined and the result showed that except for VPAF, FC and FCVL, the ACE inhibitory activity of the other nine derived peptides did not significantly change when compared with their original peptides. Surprisingly, five peptides had lower IC50values than their original peptides, particularly for RP (IC50value = 0.39 µM), which is about 30 times lower than its original peptide and almost the lowest IC50value for ACE inhibitory peptides reported. Therefore, the novel peptides identified fromA. chinensishydrolysates probably still maintain a high ACE inhibitory activity even if they are digestedin vivo. This is the first report about novel ACE inhibitory peptides from hydrolysates of marine shrimpA. chinensis. The novel peptides from hydrolysate ofA. chinensisand some of their derived peptides with high ACE inhibitory activity probably have potential in the treatment of hypertension or in clinical nutrition. Copyright © 2006 European Peptide Society and John
ISSN:1075-2617
DOI:10.1002/psc.789
出版商:John Wiley&Sons, Ltd.
年代:2006
数据来源: WILEY
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8. |
Determination of glyoxylyl‐peptide concentration using oxime chemistry and RP‐HPLC analysis |
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Journal of Peptide Science,
Volume 12,
Issue 11,
2006,
Page 734-738
Jean‐Michel Garcia,
Samia Far,
Eric Diesis,
Oleg Melnyk,
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摘要:
AbstractGlyoxylyl‐peptides are useful peptide derivatives in the context of hydrazone, oxime or thiazolidine ligations. We describe a method for the determination of glyoxylyl‐peptide concentration based on the reaction of the α‐oxo aldehyde group with an excess ofO‐benzylhydroxylamine. The amount ofO‐benzylhydroxylamine necessary to convert the α‐oxo aldehyde group into the correspondingO‐benzyloxime was determined by RP‐HPLC analysis and corresponded to the quantity of glyoxylyl‐peptide used in the experiment. The method is rapid, sensitive, accurate and allows the automated analysis of several samples. Copyright © 2006 European Peptide Society and
ISSN:1075-2617
DOI:10.1002/psc.791
出版商:John Wiley&Sons, Ltd.
年代:2006
数据来源: WILEY
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