摘要:

AbstractThe Mitsunobu reaction – the nucleophilic substitution of an alcoholic hydroxyl group mediated by the redox system trialkylphosphine/dialkyl azodicarobxylate – is widely used in the chemistry of biologically active compounds. The paper deals with applications of the Mitsunobu reaction in amino acid and peptide chemistry. The process provides easy access to many unnatural amino acids and derivatives. Since the reaction occurs with complete inversion of the configuration at the carbinol chiral centre, it can be used for the synthesis of diastereoisomers of hydroxy‒ and tioprolines. Cyclization of β‒hydroxy amino acid containing peptides under Mitsunobu reaction conditions leads to a constrained peptide that mimics the stabilizing reverse turn secondary structure. © 1998 European Peptide Society and John Wiley&

ISSN:1075-2617    

DOI:10.1002/(SICI)1099-1387(199802)4:1<1::AID-PSC132>3.0.CO;2-R

出版商:John Wiley&Sons, Ltd.    

年代:1998

数据来源: WILEY

摘要:

AbstractIon transport across phospholipid vesicles was studied by7Li and23Na‐NMR using an aqueous anionic paramagnetic shift reagent, dysprosium nitrilotriacetate [Dy(NTA)2]3−, mediated by ionophores, lasalocid A and A23187. The intra‐ and extracellular7Li and23Na‐NMR signals were well separated (20 Hz) at mMconcentration of the shift reagent. The observed data on the rate constant for lithium transport across DPPC vesicles at various concentrations of the ionophores indicated that lasalocid A is a more efficient carrier for lithium ion compared with the sodium ion transport by this ionophore, while A23187 was not specific to either of the ions (Li or Na). ©1998 European Peptide Society and John Wiley

ISSN:1075-2617    

DOI:10.1002/(SICI)1099-1387(199802)4:1<15::AID-PSC96>3.0.CO;2-E

出版商:John Wiley&Sons, Ltd.    

年代:1998

数据来源: WILEY

摘要:

AbstractThe crystal structures of three fully protected tripeptides containing the Dϕg residue (Cα,α‐diphenylglycine) in the central position are reported, namely Z‐Gly‐Dϕg‐Gly‐OMe (a), Z‐Gly‐Dϕg‐Aib‐OMe (b) and Z‐Aib‐Dϕg‐Aib‐OMe (c). The molecular conformations are quite unusual because the Dϕg residue adopts a folded conformation in the 310‐helical region when the following residue adopts a folded conformation of opposite handedness (peptidesbandc). In contrast, the Dϕg residue adopts the more frequently observed fully extended conformation when the following residue adopts a semi‐extended conformation (peptidea). These findings are in agreement with the theoretical calculations on Ac‐Dϕg‐Aib‐NHCH3and Ac‐Aib‐Dϕg‐NHCH3also reported in this work. © 19

ISSN:1075-2617    

DOI:10.1002/(SICI)1099-1387(199802)4:1<21::AID-PSC125>3.0.CO;2-A

出版商:John Wiley&Sons, Ltd.    

年代:1998

数据来源: WILEY

摘要:

AbstractTwo Tyr residues are supposed to play a crucial role in the regulation of protein tyrosine kinases of the Src family. Autophosphorylation of Src Tyr416 correlates with enzyme activation, while phosphorylation of C‐terminal Tyr527 by Csk gives rise to inactive forms of Src kinases.It has previously been demonstrated that the Src‐like tyrosine kinase expressed by the oncogenelyndisplays a particularly high affinity (Km20 μm) toward the dimeric linear and cyclic derivatives of the heptapeptide H‐Glu‐Asp‐Asn‐Glu‐Tyr‐Thr‐Ala‐OH which reproduces the main autophosphorylation site of most of the Src enzymes. Under the experimental conditions used only one Tyr residue of the dimeric sequence can be phosphorylated [P. Ruzza, A. Calderan, B.Filippi, B. Biondi, A. Donella Deana, L. Cesaro, L. A. Pinna&G. Borin (1995)Int. J. Peptide Protein Res. 45, 529–539].The present study addresses the problem of the efficiency displayed by Lyn towards the two Tyr residues located at positions 5 and 12 of the dimeric peptide. To this purpose, two tetradecapeptides were synthesized by the classical solution method, each containing one of the two Tyr residues alternatively replaced by Phe, and the corresponding univocal cyclic form. A possible correlation between the different structural properties induced by the modifications of the native sequence and the ability of the peptides to act as Lyn substrates was noted. The kinetic data obtained indicate that Lyn phosphorylates the residues located at different positions in the two linear analogues differently. In particular, while the Tyr5, Phe12 derivative presents aKmvalue similar to those obtained for the dimeric linear and cyclic unmodified analogues, theKmvalue of the Phe5, Tyr12 derivative is two‐fold higher than those found for the above‐mentioned peptides. Moreover, as previously reported for the linear and cyclic dimeric forms of the native sequence, in the mono‐tyrosine containing series of dimers the still conformationally flexible cyclic derivative shows a phosphorylation efficiency two‐fold higher than those found for the linear derivatives. © 1998 European Peptide

ISSN:1075-2617    

DOI:10.1002/(SICI)1099-1387(199802)4:1<33::AID-PSC127>3.0.CO;2-Y

出版商:John Wiley&Sons, Ltd.    

年代:1998

数据来源: WILEY

摘要:

AbstractA synthetic methodology has been developed for peptide bond formation with α‐hydroxmethylserine as the carboxyl or amino component and also for the preparation of homo‐sequences. The key intermediate, O,O‐protected α‐hydroxymethylserine in the form of an isopropylidene derivative, is easily accessible and represents the first example of a heterocyclic Cα,α‐disubstituted amino acid containing an 1,3‐dioxane ring. The use of this intermediate facilitates protection of the sterically hindered amino and carboxyl groups and is advantageous for the coupling and deprotection steps. X‐ray structure determination of Z‐HmS(Ipr)–Ala–OMe revealed that the two crystallographically independent molecules present in the asymmetric unit adopt an S‐shaped conformation. In the one molecule the achiral HmS(Ipr) residue has the torsion angle values (ϕ==61.4°,ψ=40.8°) in the left‐handed helical region of the Ramachandran map, while in the second molecule the negative torsion angles (ϕ=−60.1°, ψ=–44.4°) are associated with the right‐handed helix. © 1998 Europea

ISSN:1075-2617    

DOI:10.1002/(SICI)1099-1387(199802)4:1<46::AID-PSC128>3.0.CO;2-L

出版商:John Wiley&Sons, Ltd.    

年代:1998

数据来源: WILEY

摘要:

AbstractStepwise solution syntheses are described of the homo‐oligomers Z‐(Thr)n‐NHCH3(n=1–4,I1–4), Z‐{[Gal(Ac)4β]Thr}n‐NHCH3(n=1–5,II1–5) and Z‐[(Galβ)Thr]n‐NHCH3(n=1−5,III1–5). Members of theIII1–5series were obtained by de‐acetylation of the corresponding oligomers of theII1–5series. The conformational preferences of the terminally protected homo‐peptides of the three series were investigated by FT‐IR absorption spectroscopy both in the solid state and in CDCl3solution, at various concentrations. Proton NMR measurements in CDCl3and in DMSO‐d6were also carried out and the effect of temperature variation on the chemical shifts of amide protons was determined in DMSO‐d6(range 298–335 K) and in CDCl3(range 298–320 K). CD spectra were recorded in water and in TFE. Solubility problems prevented measurements in CDCl3solution for Z‐(Thr)4‐NHCH3and for the entireIII1–5series. The existence of unordered structures in the carbohydrate‐free oligomers and of more or less extended, organized structures in the glycosylated derivatives is indicated by the NMR and IR measurements. The sugar moieties apparently show a structure‐inducing effect on the peptide chain

ISSN:1075-2617    

DOI:10.1002/(SICI)1099-1387(199802)4:1<58::AID-PSC129>3.0.CO;2-B

出版商:John Wiley&Sons, Ltd.    

年代:1998

数据来源: WILEY

摘要:

Abstract(S‐2‐amino‐5‐(aminooxy)pentanoic acid (L‐homocanaline, HCan), a structural analogue of lysine, contains a reactive alkyloxyamine side chain and is therefore considered to react chemoselectively with carbonyl compounds by forming a kinetically stable oxime bond. The chemical synthesis ofL‐homocanaline starting from protected glutamic acid derivatives is described. Two orthogonally protected homocanaline derivatives were synthesized and their use in standard SPPS procedures was exemplified for the synthesis of a chemoselectively addressable cyclic peptide for use in TASP design. Moreover, the wide range of applications of this unique building block was demonstrated for the chemoselective ligation of an unprotected disaccharide to a HCan containing model peptide resulting in a chimeric glycopeptide structure. © 1998 European Peptide Society and John Wil

ISSN:1075-2617    

DOI:10.1002/(SICI)1099-1387(199802)4:1<72::AID-PSC130>3.0.CO;2-G

出版商:John Wiley&Sons, Ltd.    

年代:1998

数据来源: WILEY