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M Crisma

Publications and source records attributed to M Crisma.

At least 91 records · Page 5Linked to original sources
PubMed1983

Protected 1-3 segment of the peptaibol antibiotics alamethicin and hypelcin. Solid-state and solution study of a stereochemically constrained linear peptide.

A study of the modes of folding and self-association of Z-Aib-L-Pro-Aib-OMe (the protected 1-3 segment of the peptaibol antibiotics alamethicin and hypelcin) in the solid state was performed using i.r. absorption and X-ray diffraction. The stereochemically constrained tripeptide molecules adopt a 4 leads to 1 intramolecularly H-bonded form (beta-turn), where the single intramolecular H-bond is found between the peptide N-H group of the Aib3 residue and the urethane C = O group of the N-blocking benzyloxycarbonyl moiety. This folded structure is stabilized by an intermolecular H-bond between the urethane N-H group of the Aib1 residue and the peptide C = O group of the Pro2 residue of a symmetry related molecule. According to the i.r. absorption data, in CH2Cl2 and TMP solutions the same intramolecularly H-bonded form occurs as that found in solid state. Compared to the situation in the solid state, in CH2Cl2 and TMP solvation of the urethane N-H group replaces self-association (through the same N-H group). The results are also discussed in relation to those obtained for other protected -Aib-X-Aib- (X = Aib, L-Ala, L-Val) tripeptide segments of peptaibol antibiotics.

Alamethicin↗
PubMed1983

Bioorganic stereochemistry. A study of the peptide oxazolones from Z-(Aib)n-OH (n = 2-4) in the solid state.

An investigation of the preferred conformations and modes of self-association of the peptide oxazolones from Z(-Aib-)n-OH (n = 2-4) in the solid state has been performed by infrared absorption. More detailed information on the peptide oxazolone from Z(-Aib-)3OH(2) has been obtained using X-ray diffraction. In this compound the conformations of the first two Aib residues differ substantially, only the N-terminal one being found in the usual 3(10)-(or alpha-) helical region of the Ramachandran map. The C = N-bond of the oxazolone group is not conjugated with the lactone moiety. A very weak intermolecular interaction occurs between the urethane N-H and the carbonyl group of the oxazolone ring.

Aminoisobutyric Acids↗
PubMedDate not supplied

Conformational characterization of the 1-aminocyclobutane-1-carboxylic acid residue in model peptides.

A series of N- and C-protected, monodispersed homo-oligopeptides (to the dodecamer level) from the small-ring alicyclic C alpha, alpha-dialkylated glycine 1-aminocyclobutane-1-carboxylic acid (Ac4c) and two Ala/Ac4c tripeptides were synthesized by solution methods and fully characterized. The conformational preferences of all the model peptides were determined in deuterochloroform solution by FT-IR absorption and 1H-NMR. The molecular structures of the amino acid derivatives Z-Ac4c-OH and Z2-Ac4c-OH, the tripeptides Z-(Ac4c)3-OtBu, Z-Ac4c-(L-Ala)2-OMe and Z-L-Ala-Ac4c-L-Ala-OMe, and the tetrapeptide Z-(Ac4c)4-OtBu were determined in the crystal state by X-ray diffraction. The average geometry of the cyclobutyl moiety of the Ac4c residue was assessed and the tau(N-C alpha-C') bond angle was found to be significantly expanded from the regular tetrahedral value. The conformational data are strongly in favour of the conclusion that the Ac4c residue is an effective beta-turn and helix former. A comparison with the structural propensities of alpha-aminoisobutyric acid, the prototype of C alpha, alpha-dialkylated glycines, and the other extensively investigated members of the family of 1-aminocycloalkane-1-carboxylic acids (Acnc, with n = 3, 5-8) is made and the implications for the use of the Ac4c residue in conformationally constrained peptide analogues are briefly examined.

Amino Acids↗
PubMedDate not supplied

Conformational characterization of peptides rich in the cycloaliphatic C alpha,alpha-disubstituted glycine 1-aminocyclononane-1-carboxylic acid.

A series of N- and C-protected, monodispersed homo-oligopeptides (to the pentamer level) from the cycloaliphatic C alpha,alpha-dialkylated glycine 1-aminocyclononane-1-carboxylic acid (Ac9c) and two Ala/Ac9c tripeptides have been synthesized by solution methods and fully characterized. The conformational preferences of all the model peptides were determined in deuterochloroform solution by FT-IR absorption and 1H-NMR. The molecular structures of the amino acid derivatives mCIAc-Ac9c-OH and Z-Ac9c-OtBu, the dipeptide pBrBz-(Ac9c)2-OtBu, the tetrapeptide Z-(Ac9c)4-OtBu, and the pentapeptide Z-(Ac9c)5-OtBu were determined in the crystal state by X-ray diffraction. Based on this information, the average geometry and the preferred conformation for the cyclononyl moiety of the Ac9c residue have been assessed. The backbone conformational data are strongly in favour of the conclusion that the Ac9c residue is a strong beta-turn and helix former. A comparison with the structural propensity of alpha-aminoisobutyric acid, the prototype of C alpha,alpha-dialkylated glycines, and the other extensively investigated members of the family of 1-aminocycloalkane-1-carboxylic acids (Acnc, with n = 3-8) is made and the implications for the use of the Ac9c residue in conformationally constrained analogues of bioactive peptides are briefly examined.

Amino Acids, Cyclic↗
PubMedDate not supplied

Synthesis and conformational studies of peptides containing TOAC, a spin-labelled C alpha, alpha-disubstituted glycine.

A variety of host L-alanine homo-peptides (to the pentamer) containing one or two spin-labelled TOAC (2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid) residues were synthesized by solution methods and fully characterized. The conformational features of the terminally blocked, doubly spin-labelled TOAC-(Ala)2-TOAC-Ala-pentapeptide were examined in the crystal state by X-ray diffraction and in solution using a combination of techniques (Fourier transform infrared, circular dichroism, cyclic voltammetry and electron spin resonance) in comparison with singly labelled shorter peptides. The 3(10)-helical structure of the pentapeptide, promoted by the two C alpha, alpha-disubstituted glycines under favourable experimental conditions, allows an interaction to take place between the two nitroxide TOAC side chains spaced by one turn of the helix. Taken together, these results suggest that TOAC is an excellent probe for exploring bends and helices in doubly labelled peptides.

Circular Dichroism↗
PubMedDate not supplied

Inversion of 3(10)-helix screw sense in a (D-alpha Me)Leu homo-tetrapeptide induced by a guest D-(alpha Me)Val residue.

The terminally blocked tetrapeptide pBrBz-[D-(alpha Me)Leu]2-D-(alpha Me)Val-D-(alpha Me)Leu-OfBu is folded in the crystal state in a left-handed 3(10)-helical structure stabilized by two consecutive 1<--4 C = O...H-N intramolecular H-bonds, as determined by X-ray diffraction analysis. A CD study strongly supports the view that this conformation is also that largely prevailing in MeOH solution. A comparison with the published conformation of pBrBz-[D-(alpha Me)Leu]4-OfBu indicates that incorporation of a single internal beta-branched (alpha Me)Val guest residue into the host homo-tetrapeptide from the gamma-branched (alpha Me)Leu residue is responsible for a dramatic structural perturbation, i.e. an inversion of the 3(10) screw sense from right to left-handed.

Amino Acid Sequence↗
PubMedDate not supplied

Preferred conformation of peptides rich in Ac8c, a medium-ring alicyclic C (alpha,alpha)-disubstituted glycine.

A complete series of terminally blocked, monodispersed homo-oligopeptides (to the pentamer level) from the sterically demanding, medium-ring alicyclic C (alpha,alpha)-disubstituted glycine 1-aminocyclooctane-1-carboxylic acid (Ac8c), and two Ala/Ac8c tripeptides, were synthesized by solution methods and fully characterized. The preferred conformation of all the oligopeptides was determined in deuterochloroform solution by IR absorption and 1H-NMR. The molecular structures of the amino acid derivative Z-Ac8c-OH, the dipeptide pBrBz-(Ac8c)2-OH and the tripeptide pBrBz-(Ac8c)3-OtBu were assessed in the crystal state by X-ray diffraction. Conformational energy computations were performed on the monopeptide Ac-Ac8c-NHMe. Taken together, the results obtained strongly support the view that the Ac8c residue is an effective beta-turn and helix former. A comparison is also made with the conformational preferences of alpha-aminoisobutyric acid, the prototype of C (alpha,alpha)-disubstituted glycines, and of the other members of the family of 1-aminocycloalkane-1-carboxylic acids (Acnc with n = 3, 5-7) investigated so far. The implications for the use of the Ac8c residue in peptide conformational design are considered.

Amino Acids↗
PubMedDate not supplied

Self-assembling and membrane modifying properties of a lipopeptaibol studied by CW-ESR and PELDOR spectroscopies.

Trichogin GA IV is a short lipopeptaibol antibiotic that is capable of enhancing the transport of small cations through the phospholipid double layer of the membrane. The antibiotic activity of the undecapeptide is thought to be based on either its self-assembling or membrane-modifying property. The chemical equilibrium between self-aggregated and non-aggregated molecular states was studied by CW-ESR spectroscopy using solutions of TOAC nitroxide spin-labelled trichogin analogues in an apolar solvent to mimic the membrane bound state. At room temperature the two different sets of signals observed in the spectrum were attributed to the presence of both monomers and aggregates in the sample. The ESR spectra of the monomeric and aggregated forms were separated and the dependence of the fraction of monomeric peptide molecules on concentration was obtained over the range 5 x 10(-6) to 7 x 10(-4) M. A two-step aggregation mechanism is proposed: dimerization of peptide molecules followed by aggregation of dimers to assemblies of four peptide molecules per aggregate. The equilibrium constants were estimated for both steps. In addition, the lower lifetime limit was determined for dimers and tetramers. It is shown that when the peptide concentration exceeds 10(-5) M. the major part of the peptide molecules in solution has the form of tetrameric aggregates. Independently, the PELDOR technique was used to investigate the concentration dependence of the parameters of the dipole-dipole interaction between spin labels in frozen (77 K] glassy solutions of aggregates of mono-labelled TOAC analogues. The number of molecules in aggregates as well as the frequency and amplitude of PELDOR signal oscillations were found to be concentration independent in the range 5 x 10(-4) to 8 x 10(-3) M. In the frozen glassy solution state, the number of peptide molecules per aggregate was determined to be close to four, which is in agreement with the value obtained for spin-labelled trichogin at room temperature. The present data provide experimental evidence in favour of a self-assembling rather than a membrane-modifying ion conduction mechanism.

Anti-Bacterial Agents↗
PubMedDate not supplied

Constrained phenylalanine analogues. Preferred conformation of the 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) residue.

Three Tic-containing (Tic = 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) model peptides were synthesized to assess the tendency of this constrained Phe analogue to fold into a beta-bend and a helical structure, and to adopt a preferred side-chain disposition. The results of the solution conformational analysis, performed by using Fourier transform infrared absorption and 1H nuclear magnetic resonance, indicate that in chloroform the -Aib-D-Tic-Aib-, -(Aib)2-D-Tic-(Aib)2-, and -L-Pro-D-Tic- sequences fold into intramolecularly H-bonded forms to a great extent. An X-ray diffraction analysis on p-BrBz-(Aib)2-DL-Tic-(Aib)2-OMe monohydrate and p-BrBz-L-Pro-D-Tic-NHMe allows us to conclude that, while the pentapeptide methylester forms an incipient (distorted) 3(10)-helix, the dipeptide methylamide adopts a type-II beta-bend conformation. In both cases, the D-Tic side-chain conformation is D, gauche(-). The implications for the use of the Tic residue in designing conformationally restricted analogues of bioactive peptides are briefly discussed.

Fourier Analysis↗
PubMedDate not supplied

Synthesis, characterization, and solution conformational analysis of C alpha-methyl-, C alpha-benzylglycine [(alpha Me)Phe] model peptides.

We have synthesized, by solution methods, and fully characterized a variety of (alpha Me)Phe derivatives and model peptides (to the pentapeptide level). The results of the solution conformational analysis, performed by using infrared absorption and 1H nuclear magnetic resonance, support the view that the (alpha Me)Phe residue is a stronger beta-turn and helix promoter than the unmethylated Phe analog. A comparison is also made with the conclusions extracted from published work on peptides rich in other C alpha-alkylglycyl residues.

Amino Acid Sequence↗
PubMedDate not supplied

A conformation-activity study of the [L-(alpha Me)Phe]3 analog of the formyl methionyl tripeptide chemoattractant.

CHO-L-Met-L-Leu-L-(alpha Me)Phe-OMe, an analog of the formyl methionyl tripeptide chemoattractant CHO-L-Met-L-Leu-L-Phe-OH, was synthesized by solution methods and fully characterized. This compound was prepared to determine the effect of the incorporation of a conformationally restricted C alpha,alpha-disubstituted alpha-amino acid residue at position 3 on the relation of three-dimensional structure to biological activity. The peptide was tested for its ability to induce granule enzyme secretion from rabbit peritoneal polymorphonuclear leukocytes. In parallel, a conformational analysis was performed in the crystal state by x-ray diffraction and in organic solution by infrared absorption and 1H nuclear magnetic resonance. These biological and conformational data are discussed in relation to those of the prototype tripeptide and its methyl ester.

Amino Acid Sequence↗
PubMedDate not supplied

Theoretical and experimental conformational analysis of two diastereomeric "Val"-statine derivatives.

The preferred conformations and self-association modes of the two diastereomeric N-acetyl, methylamides of 3-hydroxy, 4-amino, 5-methylhexanoic acid ("Val"-statine) with (S,S) and (R,S) configurations at the 3-hydroxy and 4-amino carbon atoms, respectively, were determined in solution as well as in the crystal state by infrared absorption, 1H nuclear magnetic resonance and x-ray diffraction. A corollary conformational energy computation study was also carried out. In the crystal state intramolecular H-bonds are absent in both structures. However, the change in chirality of the carbon atom carrying the hydroxy group and the presence of a co-crystallized water molecule in the (S,S) isomer induce partially different backbone and "Val" side chain conformations and divergent intermolecular H-bonding schemes in the two isomers. A marked propensity to self-aggregate is seen in solvents of low polarity. The two isomers, however, are largely solvated in solvents of high polarity. Conformational energy computations indicate that in vacuo both diastereomers exhibit a significant flexibility and the conformers presenting absolute minima are not stabilized by any intramolecular bonding.

Amino Acid Sequence↗
PubMedDate not supplied

Conformationally restricted formyl methionyl tripeptide chemoattractants: a three-dimensional structure-activity study of analogs incorporating a C alpha,alpha-dialkylated glycine at position 2.

The conformationally restricted CHO-L-Met-Xxx-L-Phe-OY (where Xxx = Aib, Ac3c, Ac5c, Ac6c, and Ac7c; Y = H, Me) tripeptides, analogs of the chemoattractant CHO-L-Met-L-Leu-L-Phe-OH, have been synthesized in solution by classical methods and fully characterized. Compounds were compared to determine the combined effect of backbone conformational preferences and side-chain bulkiness on the relation of three-dimensional structure to biological activity. Each peptide was tested for its ability to induce granule enzyme secretion from rabbit peritoneal polymorphonuclear leukocytes. In parallel, a conformational analysis on the CHO-blocked peptide and their tertbutyloxycarbonylated synthetic precursors was performed in the crystal state and in solution using X-ray diffraction, infrared absorption, and 1H nuclear magnetic resonance. The biological and conformational data are discussed in relation to the proposed model of the chemotactic peptide receptor of rabbit neutrophils.

Alkylation↗
PubMedDate not supplied

Psi [CH2NH] backbone-modified peptides: first unequivocal observation of a C7 structure in a linear peptide.

We have elucidated the X-ray diffraction structures of the psi[CH2NH] backbone-modified analogs of Z-Pro-Leu-Gly-NH2 and t-Boc-Pro-Leu-Gly-NH2 (N alpha-protected derivatives of the tripeptide amide representing the C-terminal tail of oxytocin) with the "reduced peptide bond" located at the Pro-Leu sequence. The comparative results of these pseudopeptides show that conformational properties are similar (i.e., C7 structure at the Pro), whereas the unmodified peptides diverge substantially (i.e., t-Boc-Pro-Leu-Gly-NH2 and H-Pro-Leu-Gly-NH2 each show type-II beta-bend at the Leu-Gly; and Z-Pro-Leu-Gly-NH2 shows an open folded structure). The results for t-Boc-Pro psi[CH2NH]Leu-Gly-NH2 represent the first unequivocal proof for the existence of a C7 structure in a linear peptide.

Amino Acid Sequence↗
PubMedDate not supplied

First 3-D structure determination of a peptide oxazol-5(4H)-one with a chiral protein amino acid in the heterocyclic moiety: an x-ray diffraction analysis of the enantiomeric and racemic Goodman oxazolone.

The x-ray diffraction structure analyses of the L-enantiomeric and racemic forms of the 2-(1'-benzyloxycarbonylamino-1'-methyl) ethyl-4-benzyl-oxazol-5(4H)-one, the Goodman oxazolone, have been performed. In the crystal state the oxazolone ring of the enantiomeric compound is nearly sandwiched between the two phenyl rings, whereas in the racemate the phenyl ring of the N alpha-protecting group moves away from the oxazolone ring.

Crystallography, X-Ray↗
PubMedDate not supplied

(R)-isovaline homo-peptides adopt the left-handed 3(10)-helical structure.

A complete series of N- and C-blocked, monodispersed homo-oligopeptides from the sterically hindered (R)-isovaline residue to the hexamer level was synthesized step by step by solution methods and fully characterized. The preferred conformation of all the oligopeptides was determined in deuteriochloroform solution by Fourier transform infrared absorption and 1H nuclear magnetic resonance. In addition, the molecular structures of tripeptide, tetrapeptide and pentapeptide were assessed in the crystal state by x-ray diffraction. The results obtained confirm the conclusions from previous studies, namely that beta-bends and 3(10)-helices are preferentially adopted by isovaline-rich peptides, a clear indication that this C alpha, alpha-disubstituted glycine tends to induce folded structures much more extensively than its unmethylated parent compound alpha-aminobutyric acid. Furthermore, in this work we were able to demonstrate unambiguously for the first time that the relationship between isovaline chirality and helix screw sense is the same as that promoted by C alpha-monosubstituted glycines [(R)-amino acids give left-handed helical structures]. A comparison is also made with the conclusions extracted from published work on homo-oligopeptides from other C alpha-methylated amino acids.

Crystallography, X-Ray↗
PubMedDate not supplied

A second polymorph of a helical decapeptide.

A crystal-state structural analysis of the terminally blocked apolar decapeptide pBrBz-(Aib-L-Ala)5-OMe bis-dimethylsulfoxide solvate was performed by x-ray diffraction. The peptide molecules are basically alpha-helical with five 1<--5 C = O... H-N intramolecular H bonds. Near the C terminus the regularity of the alpha-helix is disrupted in favor of the formation of intramolecular H bonds of the 1<--4 (beta-bend) and 1<--6 (pi-bend) types. Differences in conformation, solvation and association with the published structure of the tetrahydrate decapeptide polymorph are discussed.

Chemical Phenomena↗