|
1. |
Conformational analyses of cyclic hexapeptide analogs of somatostatin containing arylalkyl peptoid and naphthylalanine residues |
|
Journal of Peptide Science,
Volume 5,
Issue 4,
1999,
Page 161-175
Ralph‐Heiko Mattern,
Thuy‐Anh Tran,
Murray Goodman,
Preview
|
PDF (181KB)
|
|
摘要:
AbstractWe report the conformational analysis by1H‐NMR in DMSO and computer simulations involving distance geometry and molecular dynamics simulations of peptoid analogs of the cyclic hexapeptidec‐[Phe11‐Pro6‐Phe7‐d‐Trp8‐Lys9‐Thr10] L‐363,301 (the numbering refers to the positions in native somatostatin). The compoundsc‐[Phe11‐Nphe6‐Nal7‐d‐Trp8‐Lys9‐Thr10] (Nphe6‐Nal7analog1),c‐[Nal11‐Nphe6‐Phe7‐d‐Trp8‐Lys9‐Thr10] (Nal11‐Nphe6analog2) andc‐[Phe11‐Nnal6‐Phe7‐d‐Trp8‐Lys9‐Thr10] (Nnal6analog3), where Nphe denotesN‐benzylglycine and Nnal denotesN‐(1‐naphthylmethyl)glycine, are subjected to SAR studies in order to investigate the influence of the bulky naphthyl aromatic ring on the conformation. TheNal11‐Nphe6andNphe6‐Nal7analogs exhibit potent binding to the hsst2, hsst3 and hsst5 receptors, whereas theNnal6analog has decreased binding affinity to all receptors but is more selective towards the hsst2 than the other two analogs and L‐363,301. The conformational search employing distance geometry, energy minimization and molecular dynamic simulations gives insight into the conformational flexibility of these analogs. The molecules adopt bothcisandtransorientations of the peptide bond between residues 11 and 6. Thecisisomers of these analogs adopt type II′ β‐turns withd‐Trp in thei+1 position and type VIaβ‐turns with thecispeptide bond between residues 6 and 11. The results of free and distance restrained molecular dynamics simulations at 300 K indicate that theNphe6‐Nal7andNal11‐Nphe6compounds adopt a preferred backbone conformation which can be described as ‘folded’ about residues 7 and 10. TheNnal6analog, which binds less effectively to the hsst receptors, has a more flexible backbone structure than theNal11‐Nphe6andNphe6‐Nal7analogs and prefers a ‘flat’ structure with regard to the orientations about Phe7and Thr10duri
ISSN:1075-2617
DOI:10.1002/(SICI)1099-1387(199904)5:4<161::AID-PSC177>3.0.CO;2-F
出版商:John Wiley&Sons, Ltd.
年代:1999
数据来源: WILEY
|
2. |
Synthesis and biological evaluation of C‐terminal hydroxamide analogues of bombesin |
|
Journal of Peptide Science,
Volume 5,
Issue 4,
1999,
Page 176-184
Chantal Devin,
Nicole Bernad,
Michèle Cristau,
Anne‐Marie Artis‐Noel,
Annie Heitz,
Jean‐Alain Fehrentz,
Jean Martinez,
Preview
|
PDF (126KB)
|
|
摘要:
AbstractBombesin pseudo‐peptide analogues containing a hydroxamide function on the C‐terminal part of the molecule, e.g. H‐D‐Phe‐Gln‐Trp‐Ala‐Val‐Gly‐His‐Leu‐NHOBzl1and H‐D‐Phe‐Gln‐Trp‐Ala‐Val‐Gly‐His‐Leu‐NHOH2were synthesized. These compounds were tested for their ability to recognize the bombesin receptor on rat pancreatic acini and on 3T3 cells, to stimulate (i) amylase secretion from rat pancreatic acini and (ii) accumulation of tritiated thymidine in 3T3 cells. Compounds1and2were able to recognize bombesin receptors on both models with high affinity (Ki=7±2 and 5.8±0.9 nmon rat pancreatic acini, andKi=4.1±1.2 and 7.7±1.9 nmon 3T3 cells, respectively). Interestingly, compound1behaved as a potent agonist in stimulating amylase secretion from rat pancreatic acini and is able to stimulate thymidine accumulation in 3T3 cells, while compound2was able to potently antagonize bombesin‐stimulated amylase secretion (Ki=22±5 nm) in rat pancreatic acini and had no proper effect on 3T3 cells; however, it was able to inhibit bombesin‐stimulated thymidine accumulation in 3T3 cells with high potency (Ki=1.6±0.6 nm). Copyright ©
ISSN:1075-2617
DOI:10.1002/(SICI)1099-1387(199904)5:4<176::AID-PSC189>3.0.CO;2-T
出版商:John Wiley&Sons, Ltd.
年代:1999
数据来源: WILEY
|
3. |
Structural requirements for cellular uptake of α‐helical amphipathic peptides |
|
Journal of Peptide Science,
Volume 5,
Issue 4,
1999,
Page 185-194
Anne Scheller,
Johannes Oehlke,
Burkhard Wiesner,
Margitta Dathe,
Eberhard Krause,
Michael Beyermann,
Mathias Melzig,
Michael Bienert,
Preview
|
PDF (128KB)
|
|
摘要:
AbstractThe structure of the cell‐permeable α‐helical amphipathic model peptide FLUOS‐KLALKLALKALKAALKLA‐NH2(I) was modified stepwise with respect to its helix parameters hydrophobicity, hydrophobic moment and hydrophilic face as well as molecular size and charge. Cellular uptake and membrane destabilizing activity of the resulting peptides were studied using aortic endothelial cells and HPLC combined with CLSM. With the exceptions that a reduction of molecule size below 16 amino acid residues and the introduction of a negative net charge abolished uptake, none of the investigated structural parameters proved to be essential for the passage of these peptides across the plasma membrane. Membrane toxicity also showed no correlation to any of the parameters investigated and could be detected only at concentrations higher than 2 μm. These results implicate helical amphipathicity as the only essential structural requirement for the entry of such peptides into the cell interior, in accord with earlier studies. The pivotal role of helical amphipathicity was confirmed by uptake results obtained with two further pairs of amphipathic/non‐amphipathic 18‐mer peptides with different primary structure, net charge and helix parameters fromI. The amphipathic counterparts were internalized into the cells to a comparable extent asI, whereas no cellular uptake could be detected for the non‐amphipathic analogues. The mode of uptake remains unclear and involves both temperature‐sensitive and ‐insensitive processes, indicating non‐endocytic contributions. Copyright © 1999 European Peptide Society an
ISSN:1075-2617
DOI:10.1002/(SICI)1099-1387(199904)5:4<185::AID-PSC184>3.0.CO;2-9
出版商:John Wiley&Sons, Ltd.
年代:1999
数据来源: WILEY
|
4. |
Comparative studies of Nsc and Fmoc asNα‐protecting groups for SPPS |
|
Journal of Peptide Science,
Volume 5,
Issue 4,
1999,
Page 195-200
Robert Ramage,
Lu Jiang,
Young‐Deug Kim,
Kevin Shaw,
Jin‐Li Park,
Hack‐Joo Kim,
Preview
|
PDF (129KB)
|
|
摘要:
Abstract2‐(4‐Nitrophenyl)sulfonylethoxycarbonyl (Nsc) is an alternative base‐labileNα‐protecting group to 9‐fluorenylmethoxycarbonyl (Fmoc) for amino acids. The UV spectrum of the Nsc group exhibits moderate absorption at 380 nm which is excellent for real‐time monitoring of the deprotection process. It also decreases the rearrangement of X‐Asp, which can be a serious problem in SPPS. Copyright © 1999 European Peptide Society and John
ISSN:1075-2617
DOI:10.1002/(SICI)1099-1387(199904)5:4<195::AID-PSC203>3.0.CO;2-G
出版商:John Wiley&Sons, Ltd.
年代:1999
数据来源: WILEY
|
|