摘要:

AbstractThe anchoring of an α‐amino‐acid derivative by its amine function on to a solid support allows some chemical reactions starting from the carboxylic acid function. This paper describes the preparation of α‐amino aldehydes linked to the support by their amine function. This was performed by reduction with LiAlH4of the corresponding Weinreb amide linked to the resin. The aldehydes obtained were then involved in Wittig or reductive amination reactions. In addition, the linked Weinreb amide was reacted with methylmagnesium bromide to yield the corresponding ketone. After cleavage from the support, the compounds were obtained in good to excellent yields and characterized. Copyright © 2004 European Peptide Society and John Wiley&S

ISSN:1075-2617    

DOI:10.1002/psc.605

出版商:John Wiley&Sons, Ltd.    

年代:2004

数据来源: WILEY

摘要:

AbstractThe distribution of an antihypertensive dipeptide, Val‐Tyr (VY), in the tissues of spontaneously hypertensive rats (SHR) was investigated in this study. A single oral administration of VY (10 mg/kg) to 18‐week‐old SHR resulted in a prolonged reduction of systolic blood pressure (SBP) up to 9 h (SBP0h198.0 ± 3.6 mmHg; SBP9h154.6 ± 3.5 mmHg). As a result of VY determination, a roughly 10‐fold higher increment of plasma VY level was observed at 1 h than that at 0 h, whereas thereafter the level declined rapidly. In tissues, VY was widely accumulated in the kidney, lung, heart, mesenteric artery and abdominal aorta with the area under the curve over 9 h of more than 40 pmol h/g tissue; of these a higher VY level was observed in the kidney and lung. In addition, a mean resident time (MRT) for each tissue (>5 h except for liver) revealed that VY preferably accumulated in the tissues rather than in the plasma (MRT 3.8 h). Significant reductions of tissue angiotensin I‐converting enzyme activity and angiotensin II level were found in the abdominal aorta as well as in the kidney, suggesting that these organs could be a target site associated with the antihypertensive action of VY. Copyright © 2004 European Peptide Society and John Wil

ISSN:1075-2617    

DOI:10.1002/psc.568

出版商:John Wiley&Sons, Ltd.    

年代:2004

数据来源: WILEY

摘要:

AbstractThe structural properties of a 10‐residue and a 15‐residue peptide in aqueous solution were investigated by molecular dynamics simulation. The two designed peptides, SYINSDGTWT and SESYINSDGTWTVTE, had been studied previously by NMR at 278 K and the resulting model structures were classified as 3:5 β‐hairpins with a type I + G1 β‐bulge turn. In simulations at 278 K, starting from the NMR model structure, the 3:5 β‐hairpin conformers proved to be stable over the time period evaluated (30 ns). Starting from an extended conformation, simulations of the decapeptide at 278 K, 323 K and 353 K were also performed to study folding. Over the relatively short time scales explored (30 ns at 278 K and 323 K, 56 ns at 353 K), folding to the 3:5 β‐hairpin could only be observed at 353 K. At this temperature, the collapse to β‐hairpin‐like conformations is very fast. The conformational space accessible to the peptide is entirely dominated by loop structures with different degrees of β‐hairpin character. The transitions between different types of ordered loops and β‐hairpins occur through two unstructured loop conformations stabilized by a single side‐chain interaction between Tyr2 and Trp9, which facilitates the changes of the hydrogen‐bond register. In agreement with previous experimental results, β‐hairpin formation is initially driven by the bending propensity of the turn segment. Nevertheless, the fine organization of the turn region appears to be a late event in the folding process. Copyright © 2004 European Peptid

ISSN:1075-2617    

DOI:10.1002/psc.564

出版商:John Wiley&Sons, Ltd.    

年代:2004

数据来源: WILEY

摘要:

AbstractThe coumarin antibiotics are potent inhibitors of DNA replication whose target is the enzyme DNA gyrase, an ATP‐dependent bacterial type II topoisomerase. The coumarin drugs inhibit gyrase action by competitive binding to the ATP‐binding site of DNA gyrase B protein. The production of new biologically active products has stimulated additional studies on coumarin–gyrase interactions. In this regard, a 4.2 kDa peptide mimic of DNA gyrase B protein fromEscherichia colihas been designed and synthesized. The peptide sequence includes the natural fragment 131–146 (coumarin resistance‐determining region) and a segment containing the gyrase–DNA interaction region (positions 753–770). The peptide mimic binds to novobiocin (Ka= 1.4 ± 0.3 × 105M−1), plasmid (Ka= 1.6 ± 0.5 × 106M−1) and ATP (Ka= 1.9 ± 0.4 × 103M−1), results previously found with the intact B protein. On the other hand, the binding to novobiocin was reduced when a mutation of Arg‐136 to Leu‐136 was introduced, a change previously found in the DNA gyrase B protein from several coumarin‐resistant clinical isolates ofEscherichia coli. In contrast, the binding to plasmid and to ATP was not altered. These results suggest that synthetic peptides designed in a similar way to that described here could be used as mimics of DNA gyrase in studies which seek a better understanding of the ATP, as well as coumarin, binding to the gyrase and also the mechanism of action of this class of antibacterial drugs. Copyright © 2004 European Peptide

ISSN:1075-2617    

DOI:10.1002/psc.565

出版商:John Wiley&Sons, Ltd.    

年代:2004

数据来源: WILEY

摘要:

AbstractThe synthesis is described of a [D‐Ala2]‐deltorphin I peptoid analogue in which all amino acid residues have been substituted by the correspondingN‐alkylglycine residues. The [D‐Ala2]‐deltorphin I retropeptoid was also prepared as well as [Ala1,D‐Ala2]‐deltorphin 1 and the corresponding peptoid. Structural investigations by FT‐IR and fluorescence measurements were carried out on the synthetic analogues and on some [D‐Ala2]‐deltorphin 1 peptide–peptoid hybrids previously prepared. According to the fluorescence measurements the distance between the aromatic residues in the deltorphin I peptoid and retropeptoid is similar to that suggested for the δ‐ and µ‐opioids, respectively. Measurements of CD in the presence of β‐cyclodextrin, and some preliminary pharmacological experiments were also performed. No dichroic bands are present in the spectrum of the [Ntyr1,D‐Ala2]‐deltorphin I, but an increasing dichroic effect appears in the spectra of both the deltorphin I peptoid and retropeptoid. Activity tests on isolated organ preparations showed that the modifications made produced a dramatic decrease in the agonistic activity of the synthetic derivatives. Copyright © 2004 European Pepti

ISSN:1075-2617    

DOI:10.1002/psc.566

出版商:John Wiley&Sons, Ltd.    

年代:2004

数据来源: WILEY