摘要:

AbstractNeuropeptide Y (NPY), peptide YY (PYY) and pancreatic polypeptide (PP) belong to the NPY hormone family and activate a class of receptors called the Y‐receptors, and also belong to the large superfamily of the G‐protein coupled receptors. Structure–affinity and structure–activity relationship studies of peptide analogs, combined with studies based on site‐directed mutagenesis and anti‐receptor antibodies, have given insight into the individual characterization of each receptor subtype relative to its interaction with the ligand, as well as to its biological function. A number of selective antagonists at the Y1‐receptor are available whose structures resemble that of theC‐terminus of NPY. Some of these compounds, like BIBP3226, BIBO3304 and GW1229, have recently been used forin vivoinvestigations of the NPY‐induced increase in food intake. Y2‐receptor selective agonists are the analog cyclo‐(28/32)‐Ac‐[Lys28‐Glu32]‐(25–36)‐pNPY and the TASP molecule containing two units of the NPY segment 21–36. Now the first antagonist with nanomolar affinity for the Y2‐receptor is also known, BIIE0246. So far, the native peptide PP has been shown to be the most potent ligand at the Y4‐receptor. However, by the design of PP/NPY chimera, some analogs have been found that bind not only to the Y4‐, but also to the Y5‐receptor with subnanomolar affinities, and are as potent as NPY at the Y1‐receptor. For the characterization of the Y5‐receptorin vitroandin vivo, a new class of highly selective agonists is now available. This consists of analogs of NPY and of PP/NPY chimera which all contain the motif Ala31‐Aib32. This motif has been shown to induce a 310‐helical turn in the region 28–31 of NPY and is suggested to be the key motif for high Y5‐receptor selectivity. The results of feeding experiments in rats treated with the first highly specific Y5‐receptor agonists support the hypothesis that this receptor plays a role in the NPY‐induced stimulation of food intake. In conclusion, the selective compounds for the different Y‐receptor subtypes known so far are promising tools for a better understanding of the physiological properties of the hormones of the NPY family and related receptors. Copyr

ISSN:1075-2617    

DOI:10.1002/(SICI)1099-1387(200003)6:3<97::AID-PSC236>3.0.CO;2-E

出版商:John Wiley&Sons, Ltd.    

年代:2000

数据来源: WILEY

摘要:

AbstractTwo cyclic disulfides of structuretsqb">Cys‐Tyr‐Arg‐Arg‐Tyr‐Cys‐NH2(1) andtsqb">Cys‐Tyr(Me)‐Arg‐Arg‐Tyr(Me)‐Cys‐NH2(2), two nonapeptide derivatives of1extended at theC‐terminal with Pro‐Arg‐Gly‐NH2(3) or Pro‐D‐Arg‐Gly‐NH2(4) and derivatives of3and4having Mpr in position 1, i.e. analogs (5) and (6), respectively, were synthesized, and their stereochemistry and biological activity were studied. All the peptides displayed low dose‐dependent uterotonic activityin vitroand antidiuretic activityin vivo. None of the peptides increased the blood pressure of the experimental animals. Compounds2,4and6showed a low inhibitory effect on AVP pressor activity; compound6, in addition, displays a significant and long‐lasting vasodepressor effect. NMR measurements indicated the existence of hydrogen bond between the amino acid residues in positions 2,5 and 3,4 of peptides1and2, and side‐chain interactions between amino acid residues in positions 2,3 and 4,5 of peptide1. No such side‐chain interactions were detected in peptide2. Copyright © 2000 E

ISSN:1075-2617    

DOI:10.1002/(SICI)1099-1387(200003)6:3<123::AID-PSC233>3.0.CO;2-H

出版商:John Wiley&Sons, Ltd.    

年代:2000

数据来源: WILEY

摘要:

AbstractBackbone cyclization has become an important method for generating or stabilizing the bioactive conformation of peptides without affecting the amino acid side‐chains. Up to now, backbone cyclic peptides were mostly synthesized with bridges betweenN‐amino‐ andN‐carboxy‐functionalized peptide bonds. To study the influence of a more flexible backbone on the biological activity, we have developed a new type of backbone cyclization which is achieved via theN‐functionalized moieties of acylated reduced peptide bonds. As described in our previous publications, the formation ofN‐functionalized dipeptide units facilitates the peptide assembly compared with the incorporation ofN‐alkyl amino acids. Besides the racemization‐free synthesis of Fmoc‐protected pseudodipeptide esters with reduced peptide bonds, the new type of backbone modification allows the use of a great variety of ω‐amino‐ and α,ω‐dicarboxylic acids differing in chain length and chemical properties. Best results for the coupling of the ω‐amino‐ and α,ω‐dicarboxylic acids to the reduced peptide bond were obtained by the formation of mixed anhydrides with alkyl chloroformates. Whereas the protecting group combination of Z/OBzl in the dipeptide unit and Boc/OtBu for theN‐functionalized moiety leads to the formation of 2‐ketopiperazine during hydrogenation, the combination of Fmoc/OtBu and Alloc/OAll is very suitable for the synthesis of backbone cyclic peptides on solid support. Copyright © 2000 Europea

ISSN:1075-2617    

DOI:10.1002/(SICI)1099-1387(200003)6:3<130::AID-PSC237>3.0.CO;2-D

出版商:John Wiley&Sons, Ltd.    

年代:2000

数据来源: WILEY

摘要:

AbstractAcetyl‐β‐(1‐azulenyl)‐D,L‐alanine has been synthesized in high overall yield by the malonic ester condensation procedure, and the racemate has been enzymatically resolved with acylase I fromAspergillus melleus. The enantiomerically pureL‐amino acid is of interest as a blue‐colored fluorescent tryptophan analog. The bioactivity data of a heptagastrin analog containing it suggests that the planar aromatic azulene moiety may indeed mimic the tryptophan side chain to some extent, and the spectral properties of the azulene moiety makes β‐(1‐azulenyl)‐L‐alanine of potential value as a UV and fluorescence probe in synthetic peptides, and possibly even in proteins if bioincorporation succeeds with chemically misacylated tRNAs. Copyright © 2000 European Peptide Society

ISSN:1075-2617    

DOI:10.1002/(SICI)1099-1387(200003)6:3<139::AID-PSC240>3.0.CO;2-6

出版商:John Wiley&Sons, Ltd.    

年代:2000

数据来源: WILEY

摘要:

AbstractThe original article to which this Erratum refers was published in Journal of Peptide Science 3(1) 1997, 47.

ISSN:1075-2617    

DOI:10.1002/(SICI)1099-1387(200003)6:3<145::AID-PSC256>3.0.CO;2-Z

出版商:John Wiley&Sons, Ltd.    

年代:2000

数据来源: WILEY