摘要:

AbstractSeveral conjugates of muramyl dipeptide (MDP) or nor‐muramyl dipeptide (nor‐MDP) with tuftsin were synthesized. Conjugates8a–fwere prepared by acylation of protected tuftsin with the isoglutamine carboxyl group of MDP or nor‐MDP2a–f. Also tuftsin analogue6(H‐Thr‐Lys‐Pro‐Arg(NO2)‐OH) was obtained. All synthesized compounds were investigated at the Medical University of Gdansk. The biological activity of the examined compounds was estimated usingin vitrocultures of human monocytes and lymphocytes. The substances displayed cytotoxic effects, as was revealed in the viability tests performed. The effects were most probably mediated by the induction of an oxidative burst in monocytes and the stimulation of redox enzymes in lymphocytes. In addition, the analogues turned out to be efficient stimulators of TNFα and IL6 secretion by monocytes and lymphocytes. Nevertheless, the secretion of cytokines did not affect the viability of the leukocyte population used in the experiments.The beneficial properties of the compounds examined (mainly6,3,8aand8c), which implies their usefulness as potential therapeutic agents, are connected with their rapid start of action and more efficient effects compared with tuftsin alone. Anin vivoassay on animal models will be performed. Copyright © 2004 European Peptide Society and

ISSN:1075-2617    

DOI:10.1002/psc.610

出版商:John Wiley&Sons, Ltd.    

年代:2005

数据来源: WILEY

摘要:

AbstractExtensive SAR studies on the unselective BRS3 agonist, [H‐D‐Phe6,β‐Ala11,Phe13,Nle14]‐bombesin‐(6‐14)‐nonapeptide amide, have highlighted structural features important for BRS3 activity and have provided guidance as to the design of selective agonists. A radically modified heptapeptide agonist, maintaining only the Trp‐Ala moiety of the parent [H‐D‐Phe6,βAla11,Phe13,Nle14]‐peptide amide, and with a very different carboxyl terminal region, has been produced which was potent at BRS3 and essentially had no NMB or GRP receptor activity. Its structure is Ac‐Phe‐Trp‐Ala‐His(τBzl)‐Nip‐Gly‐Arg‐NH2. Copyright © 2004 European

ISSN:1075-2617    

DOI:10.1002/psc.599

出版商:John Wiley&Sons, Ltd.    

年代:2005

数据来源: WILEY

摘要:

AbstractPeptide aldehydes are of interest due to their inhibitory properties toward numerous classes of proteolytic enzymes such as caspases or the proteasome. A novel access to peptide aldehydes is described using a combination of solid phase peptide synthesis with polymer‐assisted solution phase synthesis based on the oxidation of peptide alcohols with a mild and selective polymer‐bound IBX derivative. The oxidation is followed by selective purification via scavenging the peptide aldehyde in a capture‐release procedure using threonine attached to an aminomethyl resin. Peptide aldehydes are obtained in excellent purity and satisfying yield. The optical integrity of theC‐terminal residue is conserved in a high degree. The procedures are compatible with the use of common side‐chain protecting groups. The potential for using the method in parallel approaches is very advantageous. A small collection of new and known peptide aldehydes has been tested for inhibitory activity against caspases 1 and 3. Copyright © 2004 European Peptide Society and John Wiley

ISSN:1075-2617    

DOI:10.1002/psc.606

出版商:John Wiley&Sons, Ltd.    

年代:2005

数据来源: WILEY

摘要:

AbstractTwo coumarin‐labelled lysines were conveniently prepared as a fluorescence resonance energy transfer (FRET) pair for peptide cleavage detection. 7‐Methoxy and 7‐diethylamino coumarin‐3‐carboxylic acids were synthesized according to a modification of known procedures. Labelling at lysine was achieved in solution via the activeN‐hydroxysuccinimide ester of the carboxylic acid coumarin derivatives to give the target compounds in good yield. Subsequently, these modified amino acids were used in solid phase peptide synthesis (SPPS), and their potential utility in an extracellular matrix metalloprotease (MMP‐1) activity measurement via FRET and/or quenching studies was demonstrated. Copyright © 2004 European Peptide Society and John W

ISSN:1075-2617    

DOI:10.1002/psc.608

出版商:John Wiley&Sons, Ltd.    

年代:2005

数据来源: WILEY

摘要:

AbstractAn investigation of a series of single replacement analogues of PrRP‐(19–31)‐peptide has shown that good functional activity was retained when Phe31was replaced with His(Bzl), Phe(4Cl), Nle, Trp, Cys(Bzl) or Glu(OBzl); when Val28or Ile25was replaced with Phg; when Gly24was replaced withD‐Ala,L‐Ala, Pro or Sar; when Ser22was replaced with Gly and when Ala21was replaced with Thr or MeAla. The results confirm that the functionally important residues are located within the carboxyl terminal segment, ‐Ile‐Arg‐Pro‐Val‐Gly‐Arg‐Phe‐NH2. Copyright © 2004 European Peptide Societ

ISSN:1075-2617    

DOI:10.1002/psc.612

出版商:John Wiley&Sons, Ltd.    

年代:2005

数据来源: WILEY

摘要:

AbstractCathepsin D (CatD) is a member of the mammalian aspartic protease family and is involved in cellular protein degradation and in several pathological processes. A sensitive and specific assay for the determination of CatD activity in biological samples was developed. The peptide amide substrates Amca‐EDKPILF↓FRLGK(biotin)‐CONH2(I), Amca‐EEKPIC(Acm)F↓FRLGK(biotin)‐CONH2(II) and Amca‐EEKPISF↓FRLGK(biotin)‐CONH2(III) contain a CatD cleavage site (F↓F) flanked by aN‐terminal Amca‐fluorophore (7‐amino‐4‐methylcoumarin‐3‐acetic acid) and aC‐terminal biotin moiety. Substrates II and III proved to be specific substrates containing only one cleavage site for CatD. After cleavage of the Phe‐Phe bond by CatD all biotin conjugated peptides were removed with streptavidin‐coated magnetic beads. The remaining fluorescent peptides in solution represent the amount of digested substrate. The versatility of this CatD digest and pull down assay was demonstrated by measuring the activity of CatD in different subcellular fractions of human EBV‐transformed B cells and human monocytes. The described method based on the designed CatD substrates represents a valuable tool for routine assays. Copyright © 2004 Europea

ISSN:1075-2617    

DOI:10.1002/psc.607

出版商:John Wiley&Sons, Ltd.    

年代:2005

数据来源: WILEY

摘要:

AbstractA number of protected proline‐containing dipeptides Boc‐Xaa‐Pro‐OButwere converted via epimerization‐free oxidation with RuO4to dipeptides with an internal pyroglutamic acid residue, Boc‐Xaa‐Glp‐OBut. The latter were subjected to oxidative Hoffman‐type rearrangement induced by PhI[OC(O)CF3]2to giveN‐(aminoacyl)‐pyroglutamates. The behavior of these derivatives under basic conditions was studied, and for two such a derivatives an aminoacyl incorporation reaction was observed, producing otherwise poorly accessible 10‐membered‐ring dilactams derived from 1,4‐diaminobutyric and glutamic acids in practicable yields. Copyright © 2004 European Peptide Soci

ISSN:1075-2617    

DOI:10.1002/psc.611

出版商:John Wiley&Sons, Ltd.    

年代:2005

数据来源: WILEY