摘要:

The protected oligophosphoseryl peptides from bovine caseins, Z‐Xxx‐{Ser[PO(OPh)2]}3‐Glu(OBzl)‐OBzl for Xxx = Ile, Val, Gly, Leu and Ph = phenyl, were synthesized in high yields by stepwise lengthening using Boc‐Ser[PO(OPh)2]‐OH as acylating carboxyl component andN‐ethyl‐N′‐(3‐dimethylaminopropyl)‐carbodiimide hydrochloride as coupling reagent. The hydrogenolytic deprotection (PtO2) was carried out with the valine derivative and with the tetrapeptide Ser[PO(OPh)2]3‐Glu(OBzl)‐OBzl. Phosphorylation of oligoseryl peptides failed to give the expected products. Large scale phosphorylation of protected serine was carried out in the presence of triethylamine using absolute ether as a solvent. 2,2,2‐Trichloroethyl group (Tc) was shown to be a useful phosphorus protecting moiety in phosphopeptide synthesis: Boc‐Ser[PO(OTc)2]‐OBzl, Z‐Ser[PO(OTc)2]‐OBzl and Boc‐Glu(OBzl)‐Ser[PO(OTc)2]‐OBzl were synthesized in high yields using b

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1990.tb00951.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

A cyclic hexapeptide cyclo(Lys‐Gly‐Asp‐Gln‐Leu‐Ser‐) 10 was synthesized stepwise in solution by acylation of peptide ester trifluoroacetates directly with preactivated Boc‐amino acids using the DCC/HOBt method; the final cyclization reaction was performed using the pentafluorophenyl ester method in solution (1–4). This peptide is a cyclic derivative of murine tumor necrosis factor‐(127–132) and is designed as a potential antitumor agent. The cyclic peptide 10 displayed weak cytotoxic activity on three of the four human tumo

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1990.tb00952.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

A large number of reports have demonstrated the presence of neurohypophysial hormone‐like peptides in mammalian pineal glands and an antigonadotropic function has been ascribed to pineal arginine vasotocin (AVT). We have undertaken large scale purification of bovine pineal neurohypophysial hormone‐like substances which demonstrate mouse mammary milk‐ejection activity (ME‐activity)in vitro.Peptides with ME‐activity were extracted from more than 5 kg of bovine pineal glands. ME‐activity containing peptides were found in both high (Mr∼ 10 000–15 000) and low (Mr∼ 500–1000) Mrspecies from Sephadex G‐25 chromatography of 0.2nacetic acid extracts. After ultrafiltration in 5% formic acid, the neurohypophysial hormone‐like peptides were localized to an ultrafiltration Mr500–1000 retentate. A homogeneous peptide, which shared an identical retention time (RT) and amino acid sequence with synthetic 8‐arginine vasopressin (AVP), was isolated by serial semipreparative high performance liquid chromatography. On the other hand, the non‐mammalian nonap

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1990.tb00953.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The conformation of a cyclic decapeptide analog of a repeat sequence of elastin has been determined in the crystalline state using X‐ray crystallographic techniques. Tetragonal crystals were grown from a solution of the decapeptide in water; space group P42212, a = 19.439(2)&c = 13.602(1) Å, with four formula units (C40H66N10O10·4H2O) per unit cell. The cyclic decapeptide in the crystal exhibits exact twofold symmetry. The asymmetric unit contains one pentapeptide and two water molecules for a total of 32 nonhydrogen atoms. The structure has been determined by the application of direct methods and refined by full‐matrix least squares to an R index of 0.053 for 2272 reflections with intensities greater than 2σ(I). The backbone conformation of the asymmetric pentapeptide can be described as consisting of a double β bend of Type III‐I. The Type III turn has Pro (ρ= ‐59.3°, Ψ= ‐26.8°) and Ala (ρ= ‐65.9°, Ψ= ‐23.1°) at the corners while Type I turn has Ala (ρ= ‐65.9°, Ψ= ‐23.1°) and Val (ρ= ‐98.9°, Ψ= 8.3°) as the corner residues. The cyclic decapeptide has two such double b

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1990.tb00954.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

A model is proposed for the 3‐dimensional structure of endothelin, a potent vasoconstrictor and pressor peptide from vascular endothelium. The model is derived through protein structure prediction and circular dichroism studies, and is based on the atomic coordinates for the bee‐venom peptide apamin. The model derived shows the same turn‐helix motif as observed for apamin and mast‐cell degranulating peptide. On the basis of this model we suggest possible strategies for endothelin antagonist design, and note that this motif may be common in a number of peptides acting on channel p

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1990.tb00955.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The syntheses and analyses of GSSG analogues with modified ionizable groups are described. Using the mixed anhydride method, three symmetrical and three asymmetrical peptide analogues were obtained in moderate overall yields. The products were analyzed by HPLC,1H‐NMR, thin‐layer electrophoresis, and amino acid analysis. They were used to study enzyme: ligand interactions in glutathione reduct

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1990.tb00956.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Six analogs of the highly delta opioid receptor selective, conformationally restricted, cyclic peptide [d‐Pen2,d‐Pen5]enkephalin, Tyr‐d‐Pen‐Gly‐Phe‐d‐PenOH (DPDPE), were synthesized and evaluated for opioid activity in rat brain receptor binding and mouse vas deferens (MVD) smooth muscle assays. All analogs were single amino acid modifications of DPDPE and employed amino acid substitutions of known effects in linear enkephalin analogs. The effect on binding affinity and MVD potency of each modification within the DPDPE structural framework was consistent with the previous reports on similarly substituted linear analogs. Conformational features of four of the modified DPDPE analogs were examined by1H NMR spectroscopy and compared with DPDPE. From these studies it was concluded that the observed pharmacological differences with DPDPE displayed by diallyltyrosine1‐DPDPE ([DAT1]DPDPE) and phenylglycine4‐DPDPE ([Pgl4]DPDPE) are due to structural and/or conformational differences localized near the substituted amino acid. The observed enhanced μ receptor binding affinity of the carboxamide terminal DPDPE‐NH2appears to be founded solely upon electronic differences, the NMR data suggesting indistinguishable conformations. The observation that the α‐aminoisobutyric acid substituted analog [Aib3]DPDPE displays similarin vitroopioid behavior as DPDPE while apparently assuming a significantly different solution conformation suggests that further detailed conformational analysis of this analog will aid the elucidation of the key structural and conformational features required for action

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1990.tb00957.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The conformational characteristics of disulfide bridges in proteins have been analyzed using a dataset of 22 protein structures, available at a resolution of 2.0 Å, containing a total of 72 disulfide crosslinks. The parameters used in the analysis include (φ, Ψ) values at Cys residues, bridge dihedral angles χss, χ1i, χ1j, χ2iand χ2jthe distances Cαi‐Cαjand Cβi‐Cβjbetween the Cαand Cβatoms of Cys(i) and Cys(j). Eight families of bridge conformations with three or more occurrences have been identified on the basis of these stereochemical parameters. The most populated family corresponds to the “left handed spiral” identified earlier by Richardson ((1981)Adv. Protein Chem.34, 167–330). Disulfide bridging across antiparallel extended strands is observed in α‐lytic protease, crambin, and β‐trypsin and this structure is shown to be very similar to those obtained in small cystine peptides. Solvent accessible surface area calculations show that the overwhelming majority of disulfide bridge

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1990.tb00958.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Several analogs of the atrial natriuretic factor (ANF) were synthesized by the solid‐phase method using the acetamidomethyl (Acm) group for sulfhydryl protection. The compounds were tested in a receptor binding assay using bovine adrenal zona glomerulosa cell membranes and in the rat diuresis/natriuresis assay. Substitution of tyrosine in position 116 of ANF(101–126) and of the analog [3‐Mpr105]ANF(105–126)(3‐Mpr = 3‐mercaptopropionic acid) did not alter the biological activity profiles and, therefore, these two analogs in radioiodinated form will be useful for enzymatic degradation and clearance studies. Replacement of 3‐mercaptopropionic acid with 2‐mercaptopropionic acid in [3‐Mpr105]ANF(105–126) resulted in an analog with very low potency in both assay systems, presumably as a consequence of the steric bulk and/or local conformational restriction produced by the methyl group attached to the α‐carbon in position 105. The analog [3‐Mpr105, Nva109]ANF(105–126)(Nva = norvaline) showed very low affinity in the receptor binding assay but displayed considerable diuretic/natriuretic activity. The obtained biological activity profiles suggest that in comparison with other ANF peptides the des‐amino ANF(105–126) analogs may have a somewhat longer half‐lifein vivoor, alternatively, may indicate a more complex situation of ANF recept

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1990.tb00959.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The crystal structure of a tetrahydrated form ofl‐arginyl‐glycyl‐l‐aspartic acid (RGD), the consensus sequence for binding of fibrinogen to cell surface receptors, has been determined from diffractometer data. The tripeptide was crystallized in double zwitterionic form via hanging drop vapor diffusion experiments at a pH near 6.5. The orthorhombic unit cell contains four formula units in space group P212121with lattice parameters a = 4.852(4), b = 11.376(3), c = 34.083(8) Å at RT. The structure was solved by direct methods and refined to a final R = 0.067 based upon 1345 observations with I 2σ(1). Peptide bonds both aretrans, ω2= 174.2(6)° and ω3= ‐ 169.3(6)°. The backbone bends at glycine with ρ2= ‐85.5(8)°. One of the water molecules sits between the arginyl side chain and theC‐terminal carboxylate, forming an intramolecular hydrogen bond to the glycyl carboxyl and linking adjacent molecules through two other H‐bond interactions. Comparison of the structure to RGD sequences extracted from 3‐D protein structures reveals a diversity of conformations for

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1990.tb00960.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY