摘要:

Theoretical conformational analysis was carried out for several tetrapeptide analogues of β‐casomorphin and dermorphin containing a Phe residue in position 3. Sets of low‐energy backbone structures of the μ‐selective peptides [N‐Me‐Phe3,d‐Pro4]‐morphiceptin and Tyr‐d‐Orn‐Phe‐Asp‐NH2were obtained. These sets of structures were compared for geometrical similarity between themselves and with the low‐energy conformations found for the δ‐selective peptide Tyr‐d‐Cys‐Phe‐d‐Pen‐OH and nonactive peptide Tyr‐Orn‐Phe‐Asp‐NH2. Two pairs of geometrically similar conformations of μ‐selective peptides, sharing no similarity with the conformations of peptides showing low affinity to the μ‐receptor, were selected as two alternative models of probable μ‐receptor‐bound backbone conformations. Both models share geometrical similarity with the low‐energy structures of the linear μ‐selective peptide Tyr‐d‐Ala‐Phe‐Phe‐NH2.

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1991.tb00736.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

The effect of tertiary amine (DIEA) on reaction rate and product purity of a carbodiimide/HOBt‐mediated peptide synthesis was studied. It was found that very rapid activation can be achieved using carbodiimide/HOBt in non‐polar solvents, such as DCM. Although the HOBt is poorly soluble in DCM, the activation proceeds within 2 min, probably forming the HOBt‐ester. By such a preactivation followed by a coupling in the presence of DIEA the rate of coupling is comparable with other rapid methods using BOP or TBTU, and no racemization was found in a model coupling (<0.1%). For comparison, syntheses of neurotensin by means of different coupling reagents (BOP, TBTU, OPfp‐esters) and the DIEA‐catalyzed coupling after carbodiimide/HOBt‐activation under comparable conditions have shown that these procedures are of the same value in view of coupling efficiency and pro

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1991.tb00737.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

A series of [3‐tryptophan]‐β‐casomorphin‐5([Trp3]‐β‐CM‐5) analogs were investigated by circular dichroism (CD) and fluorescence spectroscopy to explore their structure‐conformation properties in solution. In addition, the comparative opioid activities of these compounds were evaluated using thein vitroguinea pig ileum (GPI) and mouse vas deferens (MVD) assays. Specifically, the pentapeptide sequence of [Trp3]‐β‐CM‐5, H‐Tyr‐Pro‐Trp‐Pro‐Gly‐OH (I) was modified at Pro‐2 and Pro‐4 byd‐Pro substitutions to provide two diastereometric analogs, [Trp3‐d‐Pro‐4]‐β‐CM‐5 (II) and [d‐Pro2,4,Trp3]‐β‐CM‐5 (III). In the GPI and MVD assays, β‐CM‐5 effected IC50values of 1.3 μmand 8.9 μm, respectively, which confirmed its known μ/δ‐selectivity on these two peripheral opioid receptor subtypes. The potencies of compounds I, II, and III were 0.2, 2.0, andIII. In summary, detailed spectroscopic analysis of three [Trp3]‐β‐CM‐5 di

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1991.tb00738.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

HCO‐Met‐Leu‐Ain‐OMe (2), an analog of the chemotactic peptide HCO‐Met‐Leu‐Phe‐OH, containing the conformationally blocked residue of the 2‐aminoindane‐2‐carboxylic acid (Ain) has been synthesized and its crystal and molecular conformation has been determined. Crystals of 2 are monoclinic, space group P21, with a = 15.059(7), b = 18.548(7), c = 9.600(4)Å;β= 85.04(3). The structure has been solved by direct methods and refined to R = 0.069 for 2813 independent reflections with I>2.5σ(I). Two independent molecules A and B have been found in the asymmetric unit of the crystal of 2. Their conformation can be described as extended at the Met and Leu residues, but folded at theC‐terminal Ain residue. The helical folding is left‐ and right‐handed in the A and B molecule, respectively. The crystal packing is characterized by ribbons of intermolecular hydrogen bonded molecules extended along the c direction. The constrained analog 2 is highly active in the superoxide production, thus indicating that a stabilization of a helical folding at theC‐terminal region of chemotactic tripeptides maintains the activity. The orientation of the aromatic ring, with respect to its adjacent backbone atoms, does no

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1991.tb00739.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

The presence of tyrosine residues in the contact area between protomers of bovine somatotropin dimers (Fernandez&Delfino,Biochem. J.209, 107‐115, 1983) was investigated taking advantage of the impaired self‐associating ability of molecules iodinated at such residues. Reaction of bovine somatotropin dissolved in 8murea with the NaI‐Chloramine T couple (2.1 × 10−4m) rendered a preparation with 3.1 iodine atoms per molecule which, by stepwise elimination of the denaturant and gel filtration through Sephadex G‐100, originated two distinguishable populations: one able (iododerivatives I), the other unable (iododerivatives II) to self‐associate. After frontal analysis, iododerivatives II were found to be unable to interact even with native molecules. Identification of the reacting tyrosine residues indicated that iodination of tyrosine 142 was responsible for the loss of the ability to form dimers in iododerivatives II. Iodohormones retained the ability to bind to somatogenic mouse hepatocyte receptors ‐ the relative potency for iododerivatives I and II being 0.60 (0.34–1.03) and 0.71 (0.41–

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1991.tb00740.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Two cyclic tetrapeptides [Boc‐cyclo(‐Xxx‐Pro‐Asn‐Lys‐)OMe (Xxx = Asp or Glu)] were synthesized and investigated by NMR spectroscopy. They were designed in order to mimic the salt bridge found in physalaemin. Isomers of the urethane bond were observed in DMSO solution. The ROESY spectrum allowed the assignment of many signals of the minor isomer of both compounds. Conformational studies based on the temperature gradients of the NH chemical shifts, coupling constants, and ROEs revealed a similar conformation for the Asp analogue as proposed for physalaemin. A β1 turn with Pro and Asn in the corner positions was found for the major isomer. No hydrogen bonds were detected for the major isomer of the cyclic Glu analogue. Molecular dynamics calculations, using the NMR based initial structures, yielded sets of conformations in agreement with the experimental data. It is concluded that the salt bridge in physalaemin is best approximated by a lactam formed from the original

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1991.tb00741.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

We have shown that two CNBr fragments of horse apocytochrome c, [Homoser‐lactone65](1–65) and (66–104), bind to the ferric heme fragment (1–25)H to form a non‐productive three‐fragment complex, and that when the heme of this complex has been kept reduced for 48 h at 25°, the peptide bond between residues 65 and 66 is restored with a yield of 24% or more. We have also shown that another CNBr fragment [Homoser‐lactone65](23–65), but not [Homoser‐lactone65](39–65), similarly rejoins to fragment (66–104) in the presence of the ferrous heme fragment with 25% or more yield. For complex of ferro‐heme fragment [Hse‐lacton65](1–65)H and apofragment (66–104) of horse cytochrome c, which restores the peptide bond between residues 65 and 66 (located on the left side of the heme) (cf. Harbury, H.A. (1978) inSemisynthetic Peptides and Proteins(Offord, R.E.&DiBello, C., eds.), pp. 73–89, Academic Press, New York), Corradin&Harbury have suggested that axial ligation of methionine 80 to the heme (on the left side) is important. Consistent with their idea, fragment [Hse80](66–104) was found not to link to [Hse‐lactone65](1–65) in the presence of ferro(1–25)H. Furthermore, the present studies indicate that the interaction involving residues 26 to 38 (on the right side) is also important for such a conformation which assists in the rejoining of the two apofragments. Combining these two ideas, we suggest that restoration of the peptide bond between residues 65 and 66 reflects the structural integrity of these complexes in the reduced form. Thus, the present reaction system can be used not only for chemical synthesis of [Homoser65] apocytochrome c but also to extend amino acid substitution stu

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1991.tb00742.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

During the recrystallization of the crude protected tripeptide ester Moz‐Asn‐Leu‐Gly‐OEt (obtained by an enzymatic coupling reaction) in methanol/water, the transesterification of this compound to methyl ester was observed. The involvement of Ca2+in this process was indicated by the results obtained in the following experiments: 1) incubation of crude Moz‐Asn‐Leu‐Gly‐OEt in methanol solutions ofo‐phenanthroline and EDTA; 2) recrystallization of the crude Moz‐Asn‐Leu‐Gly‐OEt in ethanol/water followed by incubation in methanol; 3) determination of the Ca2+content of the crude Moz‐Asn‐Leu‐Gly‐OEt. After recrystallization Moz‐Asn‐Leu‐Gly‐OEt lost the ability to be transesterified in methanol. However, in the presence of crude Moz‐Asn‐Leu‐Gly‐OEt, or calcium acetate, or a mixture of calcium chloride/sodium acetate, the compound was transesterified, suggesting that the transesterification of crude and recrystallized compounds occurs through different mechanisms. On the basis of these results, and of the conformational data obtained for these peptides by1H‐NMR, we s

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1991.tb00743.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1991.tb00744.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

[Nle7]‐endothelin was synthesized and studied by1H NMR and distance geometry calculations. The NMR study was performed first in DMSO‐d6and then in 50% acetonitrile/water since this peptide aggregates in pure water. In both cases, all spin systems were identified and assigned with the aid of two‐dimensional spectroscopy (2D): COSY (for scalar couplings) and NOESY (for dipolar couplings). On the basis of the acetonitrile/water NMR parameters, and using the DISGEO program, a three‐dimensional structure of [Nle7]‐endothelin is proposed and

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1991.tb00745.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY