摘要:

During solid‐phase peptide synthesis of homo‐oligopeptides containing leucine or alanine using the Fmoc strategy, we have observed ineffectiveN‐α‐deprotection with piperidine in a sequence‐dependent manner. Incomplete deprotection was found to be associated with subsequent slow or incomplete amino acid coupling. Optimization of the deprotection step was carried out by varying the experimental conditions e.g. deprotection time, temperature, solvents and addition of chaotropes. Coupling and deprotection steps have been investigated using color monitoring, as well as FAB MS and HPLC for product analysis. The phenomena of difficult coupling and deprotection steps in the investigated systems have been demonstrated to have the same physical chemical origins, p‐sheet formation. © Mu

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1994.tb00368.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

A detailed theoretical conformational analysis of the linear heptapeptide antibiotic [Arg2]K‐582 A (Arg‐Arg‐D‐Orn‐Thr‐D‐Om‐Lys‐D‐Tyr) was carried out. The results of the computer simulation suggest that the linear peptide has a high propensity to fold in solution into a quasi‐cyclic conformation in equilibrium with π(L‐D) helices. The synthesis of two inactive analogues with an L‐Lys in place of D‐Orn3or D‐Orn5confirms the importance of the proposed folding pattern for the occurence of the ant

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1994.tb00369.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Crystals of Eu‐(Gly‐Gly‐Gly) (H2O)5.(ClO4)3are triclinic, spacegroupPwitha=9.123 (2),b=11.185 (5),c=11.426 (2) Å; α=90.79 (2), β=98.08 (1), γ=98.57 (2)°; Z=2. The europium cation is surrounded by four oxygens from three different peptide units and four oxygens from water molecules. The geometry around the metal is a distorted bi‐capped trigonal prism. The peptide backbone conformation in this complex is compared with those in the free peptide and in various metal complexes. Considerable differences are observed between Eu(III) and Ca(II) complexes o

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1994.tb00370.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The secondary structure of amino terminal fragments of human parathyroid hormone related protein (PTHrP) in aqueous solution, in trifluoroethanol solution and in the presence of model membrane systems has been studied by circular dichroism (CD) spectroscopy. Far‐UV CD spectra of PTHrP 1–40, 1–34 amide, 7–34 amide and 1–16 are consistent with a predominantly unordered structure. Addition of trifluoroethanol stabilized α‐helical structure in the 1–34 amide and 7–34 amide peptides. The effect reached a plateau at a trifluoroethanol concentration of approximately 40%, and a helix content of some 23 residues was determined. PTHrP 1–34 amide interacted with palmitoyloleoylphosphatidyl serine vesicles and exhibited an increased α‐helix content of approximately 12 helical residues. Similar results were observed for monomyristoyllecithin micelles and sodium dodecyl sulfate micelles. No interaction with dimyristoylphosphatidylcholine vesicles was detected by CD. The ability to bind to palmitoyloleoylphosphotidyl serine vesicles was also a feature of the 1–40 and 7–34 fragments, while the 1–16 fragment was apparently unaffected by interaction with this model membrane system. These results indicate that the conformational properties of the functionally significant amino terminal 1–34 region of PTHrP parallel those reported for the corresponding, but largely nonhomologous, region of parathyroid hormone. Conformational similarities may account for the ability of PTHrP to mimic the functional prop

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1994.tb00371.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

For solid‐phase peptide synthesis, 2, 4‐dimethoxy‐4′ ‐hydroxybenzhydrol linker was prepared via lithium borohydride reduction of 2, 4‐dimethoxy‐4′‐hydroxybenzophenone. The potassium salt of the linker was coupled to chloromethylpolystyrene. This method proved to be better than use of the cesium salt. This new synthesis gave a polymer with appropriate structure and a good degre

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1994.tb00372.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The extent of transfer of the Pmc protecting group from the guanidino group of arginine to the side chain of tryptophan depends on the spacial distance of these side chains. When these two amino acids are separated by one amino acid, the transfer of the Pmc protecting group is the most pronounced, and it cannot be completely prevented by the use of currently utilized scavenger mixtures. The extent of this side reaction also depends on the amino acid separating the arginine and tryptophan residues and position of tryptophan within the peptide chain as well as on the type of the solid‐phase carrie

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1994.tb00373.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

A general synthetic method for the efficient preparation of Tyr(P) ‐containing peptides is described by the use of Fmoc‐Tyr(PO31Bu2) ‐OH in Fmoc/solid‐phase synthesis followed by simultaneous cleavage of the peptide from the resin and peptide deprotection by acidolytic treatment. The applicability of this approach is demonstrated by the synthesis of H‐Ser‐Ser‐Ser‐Tyr(P) ‐Tyr(P) ‐OH.TFA and the synthesis of the phosphorylated forms of the two physiological peptides, angiotensin II and neurotensin 8–13. In addition, the three phosphorylated peptides were used as substrates in the study of the local specificity determinants of T‐cell protein tyrosine phosphatase. In a competition assay using32P‐radiolabeled [Tyr(P)]4‐angiotensin II, both un‐labeled synthetic [Tyr(P)]4‐angiotensin II and Ser‐Ser‐Ser‐Tyr(P) ‐Tyr(P) reduced the release of32P and indicated that they efficiently competed as substrates for the phosphatase. Conversely, [Tyr(P)]4‐neurotensin 8–13 was ineffective as a competitive substrate and indicated that this particular Tyr(P) ‐containing peptide sequence was not recognized by the enzyme. The marked difference in the recognition of Asp‐Arg‐Val‐Tyr(P) ‐Ile‐His‐Pro‐Phe and Arg‐Arg‐Pro‐Tyr(P) ‐Ile‐Leu is consistent with the presence o

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1994.tb00374.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Synthesis and conformational analysis of three cyclic hexapeptides cyclo(‐Gly1‐Pro2‐Phe3‐Val4‐Xra5‐Phe6), Xaa= Phe (I), D‐Phe (II) and D‐Pro (III), were carried out to examine the influence of proline on the formation of reverse turns and the dynamics of hydrophobic peptide regions. Assignment of all1H and13C resonances was achieved by homo‐ and heteronuclear 2D‐NMR techniques (TOCSY, ROESY, HMQC, HMQC‐TOCSY and HMBCS‐270). The conformational analysis is based on interproton distances derived from ROESY spectra and homo‐ and heteronuclear coupling constants (E.COSY, HETLOC and HMBCS‐270). For structural refinements restrained molecular dynamics (MD) simulationsin vacuoand in DMSO were performed.Each peptide exhibits two conformations in DMSO solution due tocis‐transisomerism about the Gly‐Pro peptide bond. Surprisingly thecis‐Gly‐Pro segment in the minor isomers is not involved in a βVI‐turn, but forms a turn structure withcis‐Gly‐Pro in theiandi+ 1 positions. Although no stabilizing hydrogen bond is found in this turn, the φ and ψ‐angles closely correspond to a βI‐turn [Pro2:φ(i+ 1) ‐60°, ψ(i+ 1) ‐30° Phe3: φ(i+ 2) ‐100°, ψ(i+ 2) ‐50°]. Hence we call this structural element a pseudo‐βI‐turn.As expected, in the dominatingall‐transisomers proline occupies thei+ 1 position of a standard βI‐turn. Therefore,cis‐transisomerization of the Gly1‐Pro2amide bond only induces a local conformational rearrangement, with minor structural changes in other parts of the molecule. However, the geometry of the other regions is affected by the chirality

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1994.tb00375.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

A new method of synthesizingortho‐methylated phenylalanines has been developed. Phenylalanines with at least one freeortho‐position undergo a Pictet—Spengler cyclization with formaldehyde followed by hydro‐genolytic splitting of the endocyclic benzylic C—N bond of 1,2,3,4‐tetrahydroisoquinolines and afford correspondingortho‐methyl derivatives. Repeating this reaction sequence on theortho‐substituted phenylalanines yieldedortho, ortho‐disubstituted derivatives, and pro‐substituted phenylalanines yieldedortho,para‐disubstituted analogs. Our modified method of cyclization preserved the configuration at the chiral center: hydrogenolysis, on the other hand, led to racemization. Incorporation of the methylated phenylalanines into position 2 of oxytocin led to, in the case of the D‐isomers, poten

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1994.tb00376.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The duality of teleost pituitary gonadotropins was established in an advanced marine fish, the tuna (Thunnus obesus). Two different molecular forms of gonadotropins, designated tGTH I and tGTH II, were isolated from an alcoholic extract of pituitary glands following ion‐exchange chromatography and reversed‐phase HPLC. Both tGTH I and tGTH II stimulated estradiol‐17β and testosterone production in tuna ovarian folliclesin vitro, although responses to tGTH II were significantly greater than those to tGTH I. Each gonadotropin consisted of α‐ and β‐subunits. tGTH I was stable in acidic conditions, whereas tGTH II dissociated into two subunits after acid treatment. Alpha subunits of tGTH I and tGTH II had identical amino acid sequences of 94 amino acid residues. The tGTH Iβ and tGTH IIβ consisted of 102 and 115 amino acid residues, respectively, and showed 35% sequence identity. tGTH Iβ is structurally more similar to salmon GTH Iβ than to salmon GTH IIβ, whereas tGTH IIβ is more similar to salmon GTH IIβ. Thus it is evident that the tuna pituitary gland produces two chemically dis

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1994.tb00377.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY