摘要:

AbstractThe functionalization of peptides and proteins by aldehyde groups has become the subject of intensive research since the discovery of the inhibition properties of peptide aldehydes towards various enzymes. Furthermore, peptide aldehydes are of great interest for peptide backbone modification or ligation reactions. This review focuses upon their synthesis, which has been developed following two main strategies. The first strategy consists of prior synthesis of the peptide, followed by the introduction of the aldehyde function. The second possible strategy uses α‐amino aldehydes as starting materials. After protection of the aldehyde, peptide elongation occurs. At the end of the synthesis, the aldehyde function can be unmasked. Copyright © 2006 European Peptide Society and John Wiley&Sons,

ISSN:1075-2617    

DOI:10.1002/psc.787

出版商:John Wiley&Sons, Ltd.    

年代:2007

数据来源: WILEY

摘要:

AbstractGonadotropic peptides are a new generation of peptide hormone regulators of insect reproduction. They have been isolated from ovaries, oviducts, or brains of insects. The subject of this paper is insect peptides that exert stimulatory or inhibitory effects on ovarian development and oocyte maturation. On the basis of the literature data and the results of our investigations, the structure and biological properties of different groups of peptides are presented. Copyright © 2006 European Peptide Society and John Wiley&Sons, Ltd

ISSN:1075-2617    

DOI:10.1002/psc.792

出版商:John Wiley&Sons, Ltd.    

年代:2007

数据来源: WILEY

摘要:

AbstractTwo tris‐alkoxycarbonyl homoarginine derivatives, Boc‐Har{ω,ω′‐[Z(2Br)]2}‐OH and Boc‐Har{ω,ω′‐[Z(2Cl)]2}‐OH, were prepared by guanidinylation of Boc‐Lys‐OH, and used for the synthesis of neo‐endorphins and dynorphins. The results were compared with that obtained in the synthesis in which Boc‐Lys(Fmoc)‐OH was incorporated into the peptide chain, and after removing Fmoc protection, the resulting peptide‐resin was guanidinylated withN,N′‐[Z(2Br)]2‐ orN,N′‐[Z(2Cl)]2‐S‐methylisourea. The peptides were tested in the guinea‐pig ileum (GPI) and mouse vas deferens (MVD) assays. The results indicated that replacement of Arg by Har may be a good avenue for the design of biologically active peptides with increased resistance to degradation by trypsin‐like enzymes. Copyright © 20

ISSN:1075-2617    

DOI:10.1002/psc.785

出版商:John Wiley&Sons, Ltd.    

年代:2007

数据来源: WILEY

摘要:

AbstractWe have cloned, over expressed, and purified one of the two catalytic domains (residues Ala361to Gly468, ACE‐N) of human somatic angiotensin‐I converting enzyme inEscherichia coli.This construct represents theN‐catalytic domain including the two binding motifs and the 23 amino acid spacers as well as some amino acid residues before and after the motifs that might help in correct conformation. The overexpressed protein was exclusively localized to insoluble inclusion bodies. Inclusion bodies were solubilized in an 8‐Murea buffer. Purification was carried out by differential centrifugation and gel filtration chromatography under denaturing conditions. About 12 mg of ACE‐N peptide per liter of bacterial culture was obtained. The integrity of recombinant protein domain was confirmed by ESI/MS. Structural analysis using CD spectroscopy has shown that, in the presence of TFE, the ACE‐N protein fragment has taken a conformation, which is consistent with the one found in testis ACE by X‐ray crystallography. This purification procedure enables the production of an isotopically labeled protein fragment for structural studying in solution by NMR spectroscopy. Copyright © 2006 European Peptide Society and John W

ISSN:1075-2617    

DOI:10.1002/psc.788

出版商:John Wiley&Sons, Ltd.    

年代:2007

数据来源: WILEY

摘要:

AbstractTrifluoroacetate (CF3COO−, or TFA) is almost always present in commercially synthesized peptides. Unfortunately, it has a strong infrared (IR) absorption band at 1673 cm−1, significantly overlapping or even completely obscuring the amide I band of a peptide. In such cases TFA must be removed from the solution in order to be able to use IR absorption spectroscopy for peptide secondary structure determination. The most convenient and widely used procedure involves peptide lyophilization from a 0.1 M HCl solution. In our studies of the tryptophan‐rich antimicrobial peptide indolicidin, we have found that caution should be taken when using this HCl concentration. High HCl concentrations (>10 mM in unbuffered solutions and>50 mM in buffered solutions) may modify the peptide structure and reduce its thermal stability, thereby interfering with subsequent structural investigations of the peptide. Our results indicate that HCl concentrations between 2 and 10 mM are adequate to remove essentially all TFA impurities without any modification of the peptide secondary structure. Copyright © 2006 European Peptide Society and John Wiley&Son

ISSN:1075-2617    

DOI:10.1002/psc.793

出版商:John Wiley&Sons, Ltd.    

年代:2007

数据来源: WILEY

摘要:

AbstractConopeptides display prominent features of hypervariability and high selectivity of large gene families that mediate interactions between organisms. Remarkable sequence diversity of O‐superfamily conotoxins was found in a worm‐hunting cone snailConus miles. Five novel cDNA sequences encoding O‐superfamily precursor peptides were identified inC. milesnative to Hainan by RT‐PCR and 3′‐RACE. They share the common cysteine pattern of the O‐superfamily conotoxin (CCCCCC, with three disulfide bridges). The predicted peptides consist of 27–33 amino acids. We then performed a phylogenetic analysis of the new and published homologue sequences fromC. milesand the otherConusspecies. Sequence divergence (%) and residue substitutions to view evolutionary relationships of the precursors' signal, propeptide, and mature toxin regions were analyzed. Percentage divergence of the amino acid sequences of the prepro region exhibited high conservation, whereas the sequences of the mature peptides ranged from almost identical with to highly divergent from inter‐ and intra‐species. Despite the O‐superfamily being a large and diverse group of peptides, widely distributed in the venom ducts of all major feeding types ofConusand discovered in severalConusspecies, it was for the first time that the newly found five O‐superfamily peptides in this research came from the vermivorousC. miles. So far, conotoxins of the O‐superfamily whose properties have been characterized are from piscivorous and molluscivorousConusspecies, and their amino acid sequences and mode of action have been discussed in detail. The elucidated cDNAs of the five toxins are new and of importance and should attract the interest of researchers in the field, which would pave the way for a better understanding of the relationship of their structure and function. Copyright © 2006 European Peptid

ISSN:1075-2617    

DOI:10.1002/psc.802

出版商:John Wiley&Sons, Ltd.    

年代:2007

数据来源: WILEY

摘要:

AbstractSix octapeptide bombesin (BN) analogs were synthesized by substituting α‐aminoisobutyric acid (Aib), in place of Ala9or Gly11, or both, in the [D‐Phe6,desMet14]‐BN (6–14) sequence: D‐Phe6‐Gln7‐Trp8‐Ala9‐Val10‐Gly11‐His12‐Leu13‐NH2(P0). Additionally, Leu13was replaced with isoleucine in two analogs and one of the analogs was butanoylated at theN‐terminus. The antiproliferative activity of the analogs was testedin vitroon human pancreatic (MiaPaCa‐2) and colon cancer (SW620, HT29 and PTC) cell lines using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. The analogs demonstrated anticancer activity in the above cell lines at concentrations ranging from 0.01 nMto 1 µM. One of the analogs,P6, was evaluated forin vivotumor regression in a xenograft model of human primary colon cancer in athymic nude mice and was found to cause significant reduction in tumor volume. NMR and molecular dynamics (MD) simulation studies for this analog revealed the presence of a mixed 310/α‐helical structure. This study demonstrates that the designed BN analogs retain their anticancer activity after the incorporation of the constrained amino acid, Aib, and are potential molecules for future use in cancer therapy and drug targeting. Copyright © 2006 Eu

ISSN:1075-2617    

DOI:10.1002/psc.799

出版商:John Wiley&Sons, Ltd.    

年代:2007

数据来源: WILEY

摘要:

AbstractBitterness represents a major challenge in industrial application of food protein hydrolysates or bioactive peptides and is a major factor that controls the flavor of formulated therapeutic products. The aim of this work was to apply quantitative structure‐activity relationship modeling as a tool to determine the type and position of amino acids that contribute to bitterness of di‐ and tri‐peptides. Datasets of bitter di‐ and tri‐peptides were constructed using values from available literature, followed by modeling using partial least square (PLS) regression based on the threez‐scores of 20 coded amino acids. Prediction models were validated using cross‐validation and permutation tests. Results showed that a single‐component model could explain 52 and 50% of the Y variance (bitterness threshold) of bitter di‐ and tri‐peptides, respectively. Using PLS regression coefficients, it was determined that hydrophobic amino acids at the carboxyl‐terminus and bulky amino acid residues adjacent to the carboxyl terminal are the major determinants of the intensity of bitterness of di‐ and tri‐peptides. However, there was no significant (p>0.05) correlation between bitterness of di‐ and tri‐peptides and their angiotensin I‐converting enzyme‐inhibitory properties. Copyright © 2006 European Peptid

ISSN:1075-2617    

DOI:10.1002/psc.800

出版商:John Wiley&Sons, Ltd.    

年代:2007

数据来源: WILEY

摘要:

AbstractThe ubiquitous calpains, µ‐ and m‐calpain, are implicated in a variety of vital (patho)physiological processes and therefore cell‐permeable specific inhibitors represent important tools for defining the role of calpains in cells and animal models. A syntheticN‐acetylated 27‐mer peptide derived from exon B of the human calpastatin inhibitory domain 1 is known to be the most potent and selective reversible inhibitor of calpains. To improve the membrane permeability of this peptidic inhibitor, it wasN‐terminally extended with or disulfide‐linked to theC‐terminal 7‐mer fragment of penetratin, a well‐established vector for cell membrane translocation of bioactive compounds. Despite the shorter penetratin sequence, both constructs showed increased cell permeability and retained their full calpain inhibitory potency. Copyright © 2006 European Peptide Society and

ISSN:1075-2617    

DOI:10.1002/psc.790

出版商:John Wiley&Sons, Ltd.    

年代:2007

数据来源: WILEY