摘要:

AbstractTo make SPOT synthesis of peptides and their assays on glass surfaces more convenient, a simple method for making spot arrays on a slide glass was designed through patterning with a photoresist and perfluorination followed by amination with various silane compounds and polymers. With these spot‐arrayed glass surfaces, we could measure the coupling completion of each Fmoc amino acid on the glass surface by direct fluorescence analysis after fluorescence‐labeling the amino groups on the surface of each spot. Then we synthesized several types of decapeptides and HPQ‐pentapeptides on the spot‐arrayed glasses and identified the optimal surface condition for stepwise peptide coupling and on‐chip bioassay. After optimizing the surface conditions, we synthesized a model library of biotin‐Gly‐Ala‐P1‐Gly (P1: one of 19 amino acids) and successfully replicated the well‐known α‐chymotrypsin subsite specificities through Cy5‐streptavidin binding to the remaining biotin on the surface after the enzymatic digestion. Copyright © 2007 European Peptide Society

ISSN:1075-2617    

DOI:10.1002/psc.884

出版商:John Wiley&Sons, Ltd.    

年代:2007

数据来源: WILEY

摘要:

AbstractA variety of lipophilic 2‐oxoamides based on γ‐aminobutyric and δ‐aminovaleric analogues were synthesized. 2‐oxoamides containing a tetrazole, a thioethyl or a thioacetyl group are weak inhibitors of GIVA cPLA2, while derivatives containing a methyl tetrazole, a diethyl phosphonate or a thioethyl group are weak inhibitors of GV sPLA2. Copyright © 2007 European Peptide Society and John Wiley

ISSN:1075-2617    

DOI:10.1002/psc.889

出版商:John Wiley&Sons, Ltd.    

年代:2007

数据来源: WILEY

摘要:

AbstractAntifungal peptides with a molecular mass of 9 kDa and anN‐terminal sequence demonstrating remarkable similarity to those of nonspecific lipid transfer proteins (nsLTPs) were isolated from seeds of the vegetableBrassica campestrisand the mung bean. The purified peptides exerted an inhibitory action on mycelial growth in various fungal species. The antifungal activity ofBrassicaand mung bean nsLTPs were thermostable, pH‐stable, and stable after treatment with pepsin and trypsin. In contrast, the antifungal activity of mung bean chitinase was much less stable to changes in pH and temperature.BrassicaLTP inhibited proliferation of hepatoma Hep G2 cells and breast cancer MCF 7 cells with an IC50of 5.8 and 1.6 µM, respectively, and the activity of HIV‐1 reverse transcriptase with an IC50of 4 µM. However, mung bean LTP and chitinase were devoid of antiproliferative and HIV‐1 reverse transcriptase inhibitory activities. In contrast to the mung bean LTP, which exhibited antibacterial activity,BrassicaLTP was inactive. All three antifungal peptides lacked mitogenic activity toward splenocytes. These results indicate that the two LTPs have more desirable activities than the chitinase and that there is a dissociation between the antifungal and other activities of these antifungal proteins. Copyright © 2007 European Peptide Society and John Wiley

ISSN:1075-2617    

DOI:10.1002/psc.893

出版商:John Wiley&Sons, Ltd.    

年代:2007

数据来源: WILEY

摘要:

AbstractLeuprolide acetate (LA) has been accepted as treatment for prostatic cancer and is currently also being evaluated in phase II clinical trials for the treatment of Alzheimer's disease. In this study, the zinc complex of leuprolide was prepared and its structure determined by Fourier‐transform infrared (FTIR), differential scanning calorimetry (DSC), UV, X‐ray diffraction (XRD), atomic absorption spectroscopy, elemental analysis, and compared with these parameters for leuorolide acetate. Also, thein vitrorelease profile of leuprolide and its complex formin situforming implant (ISFI) in comparison to a commercial formulation (Eligard) was investigated. These studies indicate that the zinc complex can be effectively synthesized and influenced on tri‐phasic pattern after burst release of LA from the ISFI and shifts this trend to a continuous release profile. Non‐linear regression test confirmed this transformation as a zero‐order release profile as well. Copyright © 2007 European Peptide Society and John Wiley

ISSN:1075-2617    

DOI:10.1002/psc.894

出版商:John Wiley&Sons, Ltd.    

年代:2007

数据来源: WILEY

摘要:

AbstractSoft shell (SS) resins with a lightly or noncross‐linked shell layer were prepared by reducing the amount of cross‐linking agent, divinylbenzene (DVB), during seed suspension polymerization from polystyrene (PS) resin. These SS resins have a lower swelling volume than that produced by normal cross‐linking. Despite its lower swelling, however, SS (10–00) resin, which consists of the 1% DVB‐cross‐linked core and the noncross‐linked surface layer, showed higher efficiency in peptide synthesis compared with 1% DVB‐PS resin and other SS resins. Copyright © 2007 European Peptide Society and John

ISSN:1075-2617    

DOI:10.1002/psc.897

出版商:John Wiley&Sons, Ltd.    

年代:2007

数据来源: WILEY

摘要:

AbstractPaclitaxel (Pac) is the most important anticancer drug used mainly in treatment of breast, lung, and ovarian cancer and is being investigated for use as a single agent for treatment of lung cancer, advanced head and neck cancers, and adenocarcinomas of the upper gastrointestinal tract. In this work, we present the synthesis of five 2′‐paclitaxel‐substituted analogs in which paclitaxel was covalently bound to peptides or as multiple copies to synthetic carriers. Ac‐Cys(CH2CO‐2′‐Pac)‐Arg‐Gly‐Asp‐Arg‐NH2, Folyl‐Cys(CH2CO‐2′‐Pac)‐Arg‐Gly‐Asp‐Ser‐NH2, Ac‐[Lys‐Aib‐Cys(CH2CO‐2′‐Pac)]2‐NH2, Ac‐[Lys‐Aib‐Cys(CH2CO‐2′‐Pac)]3‐NH2and Ac‐[Lys‐Aib‐Cys(CH2CO‐2′‐Pac)]4‐NH2were synthesized using 2′‐halogeno‐acetylated paclitaxel derivatives. Paclitaxel conjugates showed greater solubility in water than paclitaxel and inhibited the proliferation of human breast, prostate, and cervical cancer cell lines. Although all synthesized compounds had an antiproliferative activity, the Ac‐[Lys‐Aib‐Cys(CH2CO‐2′‐Pac)]4‐NH2derivative showed improved biological activity in comparison with paclitaxel in cervi

ISSN:1075-2617    

DOI:10.1002/psc.899

出版商:John Wiley&Sons, Ltd.    

年代:2007

数据来源: WILEY

摘要:

AbstractHexapeptides such as Ac‐Arg‐Tyr‐Tyr‐Arg‐Ile‐Lys‐NH2and Ac‐Arg‐Tyr‐Tyr‐Arg‐Trp‐Arg‐NH2have been isolated from a combinatorial peptide library as small peptide ligands for the opioid peptide‐like 1 (ORL1) receptor. To investigate the detailed structural requirements of hexapeptides, 25 analogs of these hexapeptides, based on the novel analog Ac‐Arg‐Tyr‐Tyr‐Arg‐Ile‐Arg‐NH2(1), were synthesized and tested for their ORL1 receptor affinity and agonist/antagonist activity on mouse vas deferens (MVD) tissues. Analog 1 and its Cit6‐analog (10) were found to possess high affinity to the ORL1 receptor, comparable to that of nociceptin/orphanin FQ, and exhibited potent antagonist activity (pA2values of 7.77 for 1 and 7.51 for 10, which are higher than that of [NPhe1]nociceptin(1–13)‐NH2(6.90) on MVD assay. It was also found that the amino acid residue in position 5 plays a key role in agonist/antagonist activity, i.e. anL‐configuration aliphatic amino acid is required for potent antagonist activity, while a nonchiral orD‐configuration residue produces potent agonist activity. These lines of evidence may provide insight into the mechanisms controlling agonist/antagonist switching in the ORL1 receptor, and may also serve to help developing more potent ORL1 agonists and antagonists. Copyright ©

ISSN:1075-2617    

DOI:10.1002/psc.900

出版商:John Wiley&Sons, Ltd.    

年代:2007

数据来源: WILEY

摘要:

AbstractRecently we performed molecular dynamics (MD) simulations on the folding of the hairpin peptide DTVKLMYKGQPMTFR from staphylococcal nuclease in explicit water. We found that the peptide folds into a hairpin conformation with native and nonnative hydrogen‐bonding patterns. In all the folding events observed in the folding of the hairpin peptide, loop formation involving the region YKGQP was an important event. In order to trace the origins of the loop propensity of the sequence YKGQP, we performed MD simulations on the sequence starting from extended, polyproline II and native type I' turn conformations for a total simulation length of 300 ns, using the GROMOS96 force field under constant volume and temperature (NVT) conditions. The free‐energy landscape of the peptide YKGQP shows minima corresponding to loop conformation with Tyr and Pro side‐chain association, turn and extended conformational forms, with modest free‐energy barriers separating the minima. To elucidate the role of Gly in facilitating loop formation, we also performed MD simulations of the mutated peptide YKAQP (Gly → Ala mutation) under similar conditions starting from polyproline II conformation for 100 ns. Two minima corresponding to bend/turn and extended conformations were observed in the free‐energy landscape for the peptide YKAQP. The free‐energy barrier between the minima in the free‐energy landscape of the peptide YKAQP was also modest. Loop conformation is largely sampled by the YKGQP peptide, while extended conformation is largely sampled by the YKAQP peptide. We also explain why the YKGQP sequence samples type II turn conformation in these simulations, whereas the sequence as part of the hairpin peptide DTVKLMYKGQPMTFR samples type I' turn conformation both in the X‐ray crystal structure and in our earlier simulations on the folding of the hairpin peptide. We discuss the implications of our results to the folding of the staphylococcal nuclease. Copyright © 2007 European Peptide Society and Jo

ISSN:1075-2617    

DOI:10.1002/psc.907

出版商:John Wiley&Sons, Ltd.    

年代:2007

数据来源: WILEY

摘要:

AbstractA new cysteine‐based disulfide linker for Fmoc solid phase peptide synthesis was developed (Fmoc‐Cys(3‐mercapto‐3‐methylbutanoic acid)OPp) that allows the on‐resin assembly and side chain deprotection of cyclic peptides. Model peptides and a cyclic peptide library of the structure [a‐a‐x‐x‐a‐a‐c] composed ofD‐amino acids were assembled and the synthesis and cleavage conditions studied. The best cyclization results were obtained with PyBOP/HOAt/diisopropylethyl amine. Racemization rates of the cysteine in the analyzed model sequences were between 5.2 and 12.3%. Cleavage of the disulfide bond was best carried out with DTT in 50% 2‐propanol/100 mMammonium bicarbonate. The cleaved peptides can be used directly in biological assays. Copyright © 2007 European Peptide Soci

ISSN:1075-2617    

DOI:10.1002/psc.879

出版商:John Wiley&Sons, Ltd.    

年代:2007

数据来源: WILEY