摘要:

AbstractDrug discovery directed peptide research has been pursued at the IVAX Drug Research Institute (formerly Institute for Drug Research) (IDR) since the mid 1950s. Outlined are the main projects and the most significant results, which include the first synthesis of human ACTH, the discovery of GYKI‐14 166, the prototype of peptide inhibitors of thrombin, a stable anticoagulant, efegatran GYKI‐14 766, and their dual acting analogues. The identification of an agonist analogue of LHRH leading to Cetrorelix, an LHRH antagonist now in clinical use, is also presented. Copyright © 2003 European Peptide Society and John Wiley&Sons,

ISSN:1075-2617    

DOI:10.1002/psc.453

出版商:John Wiley&Sons, Ltd.    

年代:2003

数据来源: WILEY

摘要:

AbstractSince the discovery of the opioid receptors and their endogenous ligands an immense research work has been devoted to the exploration of their specificity, the mechanism of ligand binding and ligand–receptor interactions. One of the main goals has been the location and characterization of the binding sites. The present review compiles the results achieved in this field in the last quarter of a century, and puts some questions concerning the success of these efforts. Copyright © 2003 European Peptide Society and John Wiley&Sons, L

ISSN:1075-2617    

DOI:10.1002/psc.469

出版商:John Wiley&Sons, Ltd.    

年代:2003

数据来源: WILEY

摘要:

AbstractThe two diastereomeric tripeptides f‐(S)‐HmMet‐Leu‐Phe‐OMe and f‐(R)‐HmMet‐Leu‐Phe‐OMe, analogues of the prototypical chemoattractant f‐Met‐Leu‐Phe‐OH, were synthesized in solution by classical methods and fully characterized. A conformational study was performed in solution by1H‐NMR. Concomitantly, the two peptides were tested for their ability to induce chemotaxis, superoxide anion production and lysozyme secretion from human neutrophils. The conformational and biological data are discussed with regard to the proposed model of the chemotactic receptor on neutrophils. Copyright © 2003 European Peptide So

ISSN:1075-2617    

DOI:10.1002/psc.461

出版商:John Wiley&Sons, Ltd.    

年代:2003

数据来源: WILEY

摘要:

AbstractFour 19‐member synthetic peptide libraries, based on the TX1TX2T epitope motif of the mucin‐2 gastrointestinal glycoprotein (MUC2) and ranging in peptide length from dipeptides to 15‐mers (XT, TXT, TQTXT and KVTPTPTPTGTQTXT), were synthesized by combinatorial solid phase peptide synthesis using the portioning‐mixing combinatorial approach, and analysed by electrospray ionization mass spectrometry at different (1000–10 000) resolutions. Most of the components of the individual libraries could be easily identified in a single‐stage molecular mass screening experiment. The resolving power of the instrument becomes an important factor above 800–1000 Da molecular mass, when predominantly multiply charged molecular ions are formed. Approaches to the identification of isobars (glutamine/lysine), isomers (leucine/isoleucine) and sequence variations by tandem mass spectrometry, and/or by high‐performance liquid chromatography‐mass spectrometry are outlined. Copyright © 2003 European Peptide Society and Jo

ISSN:1075-2617    

DOI:10.1002/psc.462

出版商:John Wiley&Sons, Ltd.    

年代:2003

数据来源: WILEY

摘要:

AbstractThe synthesis of a high affinity mannose receptor ligand, appropriately functionalized for chemoselective ligation with an antigen or DNA‐binding moieties is described. By a combination of solid‐ and solution‐phase chemistry a versatile synthesis of the target structure was accomplished. Examples of subsequent ligation reactions are described. Copyright © 2003 European Peptide Society and John Wiley&Son

ISSN:1075-2617    

DOI:10.1002/psc.463

出版商:John Wiley&Sons, Ltd.    

年代:2003

数据来源: WILEY

摘要:

AbstractSequence‐specific nuclear magnetic resonance (NMR) assignments have been determined for the peptide αS2‐CN(2–20) containing the multiphosphorylated motif‐8Ser(P)‐Ser(P)‐Ser(P)‐Glu‐Glu12‐ in the presence of molar excess Ca2+. The secondary structure of the peptide was characterized by sequential (i,i + 1), medium‐range (i,i + 2/3/4) nOes and Hα chemical shifts. Molecular modelling of the peptide based on these constraints suggests a nascent helix for residues Ser(P)9to Glu12. The spectral data for αS2‐CN(2–20) were compared with those of other casein phosphopeptides β‐CN(1–25) and αS1‐CN(59–79) that also contain the multiphosphorylated motif. This comparison revealed a similar pattern of secondary amide chemical shifts in the multiphosphorylated motif. However, the patterns of medium‐range nOe connectivities in the three peptides suggests they have distinctly different conformations in the presence of Ca2+despite having a high degree of sequential similarity. Copyright © 2003 European P

ISSN:1075-2617    

DOI:10.1002/psc.465

出版商:John Wiley&Sons, Ltd.    

年代:2003

数据来源: WILEY

摘要:

AbstractTwelve analogues were synthesized, their structure derived from modifications of [(S)Pmp1,D‐Trp2, Pen6, Arg8]oxytocin, PA, in which (S)Pmp = β,β‐(3‐thiapentamethylene‐β‐mercaptopropionic acid). PA is a potent antagonist of the uterotonic effect of oxytocin in the rat (uterotonic testin vitro, pA2= 8.86) and in the baboon. Truncated analogues of PA from theC‐terminus were systematically prepared ending in either the free acid or the amide, i.e. PA1–9acid, PA1–8acid, PA1–7acid, PA1–6acid, PA1–8amide, PA1–7amide and PA1–6amide. PA1–8amide was roughly as potent as PA in the rat uterotonic assayin vitro, and the shorter amides were only somewhat weaker antagonists. All four acid analogues were weaker antagonists than PA but still maintained rather high antagonistic potency. These findings suggest that, if these truncated acids form as metabolitesin vivo,they may contribute to the overall biological effect of PA and their contribution should be taken into account. Furthermore, using these analogues, the radioimmunoassay measurements of PA may be standardized, as they may cross react with PA antibodies and interfere with the determination. In addition, five analogues were made by substituting Arg8of PA with Lys8, Orn8, Dab8, Dap8and Cit8. All of these analogues maintained high potency as OTAs in the uterotonic assay, although their activity was only about 1.5–3 times lower than PA. The most potent analogue in the uterotonic assay, [Dap8]PA, pA2= 8.53, had weak pressor activity (pA2= 6.90) and no antidiuretic effect. The pressor activity was lower for all tested acids, and for PA1–6acid it was even below the detection limit. Additionally, PA1–9acid, PA1–7acid and PA1–6acid showed no antidiuretic activity. Hence, the PA1–6acid is a potent OTA with pA2= 8.27 and no measurable effect in the pressor or antidiuretic tests and thus it is a pure oxytocin antagonist. This fact makes it an attractive candidate for further studies on inhibition of OT biological effects and on preterm labour. Copyright © 2003 Europe

ISSN:1075-2617    

DOI:10.1002/psc.471

出版商:John Wiley&Sons, Ltd.    

年代:2003

数据来源: WILEY