摘要:

AbstractThe effects of replacingL‐pyroglutamic acid with the cyclopropane analogue 2,3‐methanopyroglutamic acid (2,3‐MeGlp) on conformation and enzymatic stability have been investigated in 2,3‐MeGlp‐NHMe and the novel thyrotropin releasing hormone (TRH) analogue [2,3‐MeGlp1]‐TRH by x‐ray diffraction and nmr. While 2,3‐MeGlp‐NHMe adopts a folded conformation (small ψ angle) in the solid state, several conformations are available to the molecule in solution.1H‐nmr of the diastereomeric mixture [(±)‐2,3‐MeGlp1]‐TRH indicates a close orientation of the pyrrolidone and imidazole rings. The 2,3‐MeGlp‐His amide bond is considerably more stable to pyroglutamate aminopepti

ISSN:0006-3525    

DOI:10.1002/bip.360280114

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractThe third and fifth aromatic residues of dermorphin, a potent μ‐opioid peptide, and of its N‐terminal fragments, from the pentapeptide to the parent heptapeptide amide, have been systematically substituted with Z‐dehydrophenylalanine (Δ‐Phe) and/or Phe to investigate the conformation–activity relationship.The characterization in DMSO‐d6at 500 MHz indicates that, in this solvent, all peptides adopt essentially random, extended conformations, as a consequence of the strong solvation. The chemical shift of the methyl group ofD‐Ala is influenced by the precise orientation of the side chain of the third residue in a fashion that can be correlated to the μ potency, consistently with our model of μ‐receptor.However, the complexes of the pentapeptides with 18‐crown‐6‐ether, when dissolved in chloroform, adopt ordered, folded conformations, a behavior that closely parallels the CD

ISSN:0006-3525    

DOI:10.1002/bip.360280115

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractThe protected tripeptidetert‐butyloxycarbonyl‐L‐leucyl‐L‐aminosuccinyl‐L‐phenylalaninamide crystallizes in the orthorhombic space group P212121, witha= 6.214(3),b= 12.832(3),c= 33.094(4) Å,Z= 4. The structure was solved by direct methods using MULTAN 80 and refined to anRvalue of 0.055 for 1458 reflections. The bond lengths and angles are in good agreement with the standard values. The peptide backbone adopts a type II′ β‐bend conformation with a weak intramolecular hydrogen bond between the CO group of the leucyl residue and the C‐terminal NH2group. In agreement with previous studies, this structure confirms the high propensity of aminosuccinyl peptides to adopt a type II′ β‐bend conformation. The role of this conformation in relation to the deamidation process in

ISSN:0006-3525    

DOI:10.1002/bip.360280116

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractIn view of the chemical and structural interest of cyclopeptides bearing an electron withdrawing substituent directly bonded at the amide nitrogen atom, the two N‐p‐toluensulfonyl (N‐tosyl) derivatives cyclo[‐Phe(Tos)‐D‐Phe‐] (I) and cyclo[‐Phe(Tos)‐D‐Pro‐] (II) have been synthesized and their stereochemistry defined. The molecular structure of I, as determined by x‐ray diffraction analysis, is reported together with1H‐nmr parameters indicating the preferred rotameric conformation in chloroform solution. The N‐tosyl group alters the geometry of the cyclodipeptide ring by lengthening both the NC bonds departing from the tosylated nitrogen and reducing the corresponding ring angle. The 6‐membered peptide ring adopts an unusual “sofa” conformation with the Tos‐Phe Cαatom deviating 0.230(3) Å out of the mean plane of the other five ring atoms. One of the two SO bonds forms a planar system that involves the tosylated nitrogen and the corresponding amide carbonyl. In the crystal, both the benzylic side chains are folded over the heterocyclic ring, whereas in chloroform solution, the benzylic side chain of

ISSN:0006-3525    

DOI:10.1002/bip.360280117

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractCombinations ofL‐ andD‐proline residues are useful compounds for finding new structures and properties of cyclic peptides. This is demonstrated with one striking example, the cyclic tetrapeptide c(D‐Pro‐L‐Pro‐D‐Pro‐L‐Pro). For this molecule composed of strictly alternatingD‐ andL‐configurated residues, a highly symmetrical structure is expected, which should be an optically inactive meso‐form. Cyclization of the enantiomeric pure linear precursorD‐Pro‐L‐Pro‐D‐Pro‐L‐Pro, however, yields a racemic mixture of two enantiomeric cyclotetrapeptides, both with twofold symmetry and acis–trans–cis–transsequence of the peptide bonds. Remarkably, this formation of a racemate was not caused by racemization, but bycis/transisomerization of all peptide bonds in the ring. This process may occur in the linear precursor during the ring formation (cyclization of conformers withtrans–cis–transorcis–trans–cisarrangement of the amide bonds) as well as in the enantiomeric pure cyclic tetrapeptide at higher temperature. In the latter case, an all‐cisstructure should exist as the intermediate, which can form acis–trans–cis–transsequence in two equivalent ways, leading finally to two enantiomeric cyclotetrapeptides. In the first one, thecispeptide bonds are attributed to theL‐residues and thetranspeptide bonds to theD‐residues; in the second one, thecisbonds belong to theDand thetransbonds to theL‐residues. The mixture of these two enantiomers does not crystallize in the racemic form, but in enantiomeric pure separate crystals. The structural properties could be proved by1H‐ and13C‐nmr spectroscopy and x‐ray analysis. Thecis/transisomerization process was confirmed by optical rotation measurements and CD spectroscopy, as well as DREIDING model studies. Calorimetric measurements in the solid state suggest the existence of the expected all‐cisintermediate. The backbone conformation of the 12‐membered medium‐sized ring shows only slight deviations—up to 6° —from the planarity of the peptide bonds. On the other hand, th

ISSN:0006-3525    

DOI:10.1002/bip.360280118

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractThe crystal‐state molecular structures of five linear Ac3c homo‐oligopeptides to the tetramer were determined by x‐ray diffraction. The oligomers are H‐(Ac3c)2‐OMe, Fmoc‐(Ac3c)2‐OMe MeOH, Ac‐(Ac3c)2‐OMe,pBrBz‐(Ac3c)3‐OMe · H2O, andt‐Boc‐(Ac3c)4‐OMe · 2H2O. The results indicate the propensity of the tri‐ and tetrapeptides to fold into type I β‐bends anddistorted310‐helices, respectively, in partial contrast to Aib, Ac5c, and Ac6c homo‐peptides of comparable main‐chain length, whereregulartype III β‐bends and 310‐helical structures were found. When the influence of the constraints produced by the intramolecular H bonds of the C10‐type is absent, other less common structural features may be observed. The average geometry of the cyclopropyl group of the Ac3c residue is found to be asymmetric and the NCαC′ bond angle sig

ISSN:0006-3525    

DOI:10.1002/bip.360280119

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractThe possibility of selectively reducing the number of β‐helical structures theoretically possible for aD,L‐alternating peptide by using a N‐methyl group as conformational constraint is considered. Some1H‐nmr data regarding Boc(L‐Nle‐D‐Nle)3‐L‐Nle‐D‐MeNle‐L‐Nle‐D‐Nle‐L‐Nle‐OMe (I), its formyl analogue (II), and the pentadecapeptide Boc(D‐Leu‐L‐Leu)5‐D‐MeLeu‐(L‐Leu‐D‐Leu)2‐OMe (III) are presented. It is shown that these alternating stereocooligopeptides with a N‐methyl group in the (n− 3) (I and II) or (n− 4) position (III) differ drastically in their behavior from the corresponding nonmethylated compounds. In chloroform, I and II form predominantly ↑↓ β7.2‐helices and III forms almost exclusively ↑↓ β5.6or ↑↓ β7.2‐helices. The helices

ISSN:0006-3525    

DOI:10.1002/bip.360280120

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractThe structure of Boc‐(L‐Val‐D‐Val)4‐OMe has been determined by x‐ray single‐crystal diffraction analysis. The octapeptide crystallizes in the trigonal system, space group P3221 witha=b= 12.760 Å,c= 63.190 Å andZ= 6. The independent unit is represented by one octapeptide chain. The structure has been solved by direct methods and it was anisotropically refined by least‐squares procedures to a finalRvalue of 0.08 for the 3018 “observed” reflections. One molecule of water was also located in the unit cell. Two octapeptide chains, related by a crystallographic binary axis, wind up around each other giving rise to a double‐stranded left‐handed antiparallel ↑↓ β5.6‐helix. The dimer, stabilized by 14 interstrand NH ⃛OC hydrogen bonds, can be regarded as a cylinder with an hydrophilic inner core represented by the peptide units and an hydrophobic exterior of isopropyl groups. The i

ISSN:0006-3525    

DOI:10.1002/bip.360280121

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractThe crystal structure of Boc‐(L‐Phe‐D‐Phe)4‐OMe has been determined by x‐ray diffraction analysis. The peptide crystallizes in the triclinic system, space group P1 witha= 15.290 Å,b= 15.163 Å,c= 19.789 Å, α = 102.49°, β = 96.59°, γ = 74.22°, and Z = 2. The structure has been solved by coupling of the molecular replacement technique and expansion by tangent formula refinement of the set of known phases. Several cycles of Fourier calculations and least‐squares refinement led to the location of 194 atoms of the two independent octapeptide chains and few molecules of cocrystallized solvent (chloroform, water, and methanol). The isotropic refinement converged toR= 0.13 for the 3077 “observed” reflections.The two independent octapeptide molecule form a dimer in the solid state: the two chains are associated by interstrand hydrogen bonds (12 of the the type NH ⃛OC) with the formation of a double‐stranded antiparallel right‐handed ↑↓ β5.6‐helix. These double helices can be represented as a cylinder with a hydrophilic inner core represented by the peptide units and an hydrophobic exterior constituted by the aromatic moieties. The dimensions of the cylinder are equal to those observed for Boc‐(L‐Val‐D‐Val)4‐OMe. In the solid state the dimers pack with each other in an hexagonal fashion with the formation of layers; be

ISSN:0006-3525    

DOI:10.1002/bip.360280122

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractIn the present paper we describe the single‐crystal x‐ray analyses of two cyclic hexapeptides containing an equal number of alternating L,D‐residues as putative analogues of the metal binding compounds, enniatin and beauvericine. Both the molecules of c(L‐Val‐D‐Val)3and c(L‐Phe‐D‐Phe)3retain in the solid state the center of symmetry and crystallize with six and eight trifluoroacetic acid molecules, respectively. The peptides are strongly hydrogen bonded to the solvent molecules. We estimate, on the basis of the molecular geometry and spatial arrangement of the peptide carbonyl groups and in comparison with other metal binding cyclic peptides, the ability of these molecules to interact with metal ions

ISSN:0006-3525    

DOI:10.1002/bip.360280123

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY