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V Moretto

Publications and source records attributed to V Moretto.

16 recordsLinked to original sources
PubMed2004

New tools for the control of peptide conformation: the helicogenic Calpha-methyl, Calpha-cyclohexylglycine.

The novel Calpha-tetrasubstituted alpha-amino acid Calpha-methyl, Calpha-cyclohexylglycine was prepared by hydrogenation of its Calpha-methyl, Calpha-phenylglycine precursor. Terminally protected homodi-, homotri-, and homotetrapeptides from Calpha-methyl, Calpha-cyclohexylglycine and co-oligopeptides to the pentamer level in combination with Gly or alpha-aminoisobutyric acid residues were prepared by solution methods and fully characterized. The results of a conformational analysis, performed by use of Fourier transform infrared (FT-IR) spectrophotometer absorption, 1H NMR, and X-ray diffraction techniques, support the contention that this Calpha-methylated, Cbeta-trisubstituted aliphatic alpha-amino acid is an effective beta-turn and 3(10)-helix inducer in tri- and longer peptides as its Calpha-methyl valine parent compound, but partially divergent from the corresponding aromatic Calpha-methyl, Calpha-diphenylmethylglycine residue, known to promote folded and fully extended structures to a significant extent in these oligomers.

Alanine↗
PubMed2001

Partial [alphaMe]Aun scan of [l-Leu11-OMe]-trichogin GA IV, a membrane active synthetic precursor of the natural lipopeptaibol.

We synthesized using solution-phase methods three analogs of [l-Leu11-OMe] trichogin GA IV, a membrane active synthetic precursor of the lipopeptaibol antibiotic in which the N-terminal n-octanoyl group and each of the three Aib residues in positions 1, 4 and 8 are replaced by an acetyl group and the lipophilic Calpha,alpha-disubstituted glycine l-(alphaMe)Aun, respectively [partial (alphaMe)Aun scan]. FT-IR absorption and CD analyses unequivocally show that the main three-dimensional structural features of [l-Leu11-OMe] trichogin GA IV are preserved in the analogs. Also, [l-Leu11-OMe] trichogin GA IV and the three Nalpha-acetylated l-(alphaMe)Aun analogs exhibit strictly comparable membrane-modifying properties. Taken together, these results strongly favor the conclusion that a shift of the long hydrocarbon moiety from the Nalpha-blocking group to the side-chain of the 1, 4 or 8 residue does not have any significant effect on the conformational properties or the membrane activity of [l-Leu11-OMe] trichogin GA IV and, by extension, of the natural lipopeptaibol.

Anti-Bacterial Agents↗
PubMed2001

Disaccharide modulation of the mitochondrial membrane fluidity changes induced by the membrane potential.

The influence of the medium composition on the dynamic properties of mitochondrial membranes on depolarization was studied by following the fluorescence anisotropy changes of mitochondria-bound 1,6-diphenyl-1,3,5-hexatriene (DPH) and hematoporphyrin (HP) as reporters, respectively, of lipid and protein regions. On collapse of the potential, the membrane fluidity increased in NaCl-, KCl-, and monosaccharide-based media and decreased in disaccharides. Infrared spectroscopy experiments suggested that disaccharides likely change water's structure and association on the membrane surface. These results indicate that disaccharides induce membrane perturbation, which may interfere in the study of structure-function correlation in biological membranes.

Animals↗
PubMed2000

Preferred conformation of peptides based on cycloaliphatic C(alpha,alpha)-disubstituted glycines: 1-amino-cycloundecane-1-carboxylic acid (Ac11c).

Two complete series of N-protected oligopeptide esters to the pentamer level from 1-amino-cycloundecane-1-carboxylic acid (Ac11c), an alpha-amino acid conformationally constrained through a medium-ring C(i)alpha<-->C(i)alpha cyclization, and either the L-Ala or Aib residue, along with the N-protected Ac11c monomer and homo-dimer alkylamides, have been synthesized by solution methods and fully characterized. The preferred conformation of these model peptides has been assessed in deuterochloroform solution by FT-IR absorption and 1H-NMR techniques. Furthermore, the molecular structures of one derivative (Z-Ac11c-OH) and two peptides (the tripeptide ester Z-Aib-Ac11c-Aib-OtBu and the pentapeptide ester Z-Ac11c-(Aib)2-Ac11c-Aib-OtBu) have been determined in the crystal state by X-ray diffraction. The experimental results support the view that beta-bends and 3(10)-helices are preferentially adopted by peptides rich in Ac11c, the second largest cycloaliphatic C(alpha,alpha)-disubstituted glycine known. This investigation has allowed the authors to approach the completion of a detailed conformational analysis of the whole 1-amino-cycloalkane-1-carboxylic acid (Ac(n)c, with n = 3-12) series, which represents the prerequisite for their recent proposal of the 'Ac(n)c scan' concept.

Acids, Carbocyclic↗
PubMed1993

First characterization at atomic resolution of the C-activating groups in a peptide synthesis acid chloride, acid azide and carboxylic-carboxylic mixed anhydride.

The X-ray diffraction structures of three N alpha-protected, C alpha-activated MeAib derivatives are reported. They are Tos-MeAib-Cl, Tos-MeAib-N3 and Tos-MeAib-O-Piv. The geometry and conformation of these classical carboxyl activating groups, which have been characterized at atomic resolution for the first time, are discussed.

Anhydrides↗
PubMed1992

Monomer units for the beta-bend ribbon structure: MeAib peptides.

A conformational analysis in CDCl3 solution by using i.r. absorption and 1H nuclear magnetic resonance spectroscopy was performed on the fully blocked dipeptides Z-MeAib-Aib-NHMe, Z-MeAib-L-Ala-NHMe, Z-Aib-MeAib-NHMe, and Z-L-Ala-MeAib-NHMe, representing repeating units of the beta-bend ribbon spiral (an approximate 3(10)-helix, with an intramolecular H-bonding donor every two residues), where Z represents benzyloxycarbonyl, MeAib alpha-methylaminoisobutyric acid, and NHMe methylamino. The molecular and crystal structures of the first three compounds were also assessed by X-ray diffraction. While the -MeAib-Aib-, -MeAib-L-Ala-, and -Aib-MeAib- sequences give stable beta-bend structures, the preferred conformation of the -L-Ala-MeAib- sequence is open. These results indicate that the MeAib residue is a good beta-bend promoter, but less efficient than its unmethylated counterpart at position i + 2.

Dipeptides↗
PubMed1991

GC-rich DNA sequences block homologous recombination in vitro.

The capacity of the RecA protein of Escherichia coli to promote an essential step in homologous recombination, strand transfer, was tested on DNA substrates varying in percentage GC. GC content was determined by a novel method using the polymerase chain reaction. Strand transfer activity is greatly reduced as a function of increasing GC content of the DNA. Some reduction is observed with substrates having a GC percentage similar to that of E. coli. The transfer reaction between sequences adjacent, but not distal, to GC-rich sequences is similarly decreased, suggesting that the structure of RecA-DNA complexes may differ with the GC content of DNA. Our results implicate an important role of DNA sequence in homologous recombination and suggest that many sequences are excluded due to their GC content.

Base Composition↗
PubMed1990

N alpha-formylated and tert-butyloxycarbonylated Phe-(Leu-Phe)n and (Leu-Phe)n peptides as agonists and antagonists of the chemotactic formylpeptide receptor of the rabbit peritoneal neutrophil.

The various diastereomers of the N alpha-formylated(CHO) and tert-butyloxycarbonylated (t-Boc) Phe-(Leu-Phe)n and (Leu-Phe)n methyl esters, where n = 1-2 and 1-3, respectively, have been newly synthesized and their physical properties described. The CHO-blocked peptides are all able to release beta-glucosaminidase from rabbit peritoneal neutrophils in a concentration-dependent manner. There is a strong effect of primary structure and of chirality on their biology activity; lengthening the peptide chain distinctly increases activity in each series and within a series the activity decreases in the order: all-L greater than D-L much greater than all-D. Of the t-Boc protected synthetic precursors, the all-L isomers have definite but weak agonist activity; the agonist activity of the other isomers is equivocal or not detectable. All the t-Boc peptides, however, are capable of acting as weak, specific antagonists. There is a dependence of antagonist activity on primary structure, but this is variable and contingent on the nature of the peptide. Similarly, an effect of chirality on antagonist activity, although present, also depends on the structure of the peptide. In the one instance directly tested, t-Boc-L-Phe-(D-Leu-L-Phe)2-OMe (OMe, methoxy) was found to be distinctly less active than the corresponding free acid.

Amino Acid Sequence↗
PubMed1990

Plus-origin mapping of single-stranded DNA plasmid pE194 and nick site homologies with other plasmids.

Staphylococcus aureus plasmid pE194 manifests a natural thermosensitivity for replication and can be established in several species, both gram positive and gram negative, thus making it attractive for use as a delivery vector. Like most characterized plasmids of gram-positive bacteria, pE194 generates single-stranded DNA. The direction of pE194 replication is clockwise, as determined by the strandedness of free single-stranded DNA. Significant homology exists between a 50-base-pair sequence in the origin of pE194 and sequences present in plasmids pMV158 (Streptococcus agalactiae), pADB201 (Mycoplasma mycoides), and pSH71 (Lactococcus lactis). We used an initiation-termination reaction, in which pE194 initiates replication at its own origin and is induced to terminate at the related pMV158 sequence, to demonstrate that pE194 replicates by a rolling-circle mechanism; the initiation nick site was localized to an 8-base-pair sequence.

Base Sequence↗
PubMed1985

Self-association and solubility of peptides. Solvent-titration study of protected C-terminal segments of porcine secretin.

Self-association of peptides (related to the C-terminal sequence of porcine secretin) in methylene chloride was disrupted by adding dimethylsulfoxide in increasing amounts. This structural transition was monitored by the disappearance of the amide-I C = O stretching band of strongly intermolecularly hydrogen-bonded molecules (1625-1630 cm-1) in the infrared absorption spectra. The effects induced by main-chain length and sequence, type of N alpha-protection, and concentration were assessed. Hexamethylphosphortriamide was compared for its structure-disrupting properties to dimethylsulfoxide. The increasing propensity to aggregate displayed by these peptides is paralleled by a decrease in their solubility. The impact of these results on the planning of peptide syntheses is briefly discussed.

Animals↗
PubMed1983

Conformational characteristics of homo-oligopeptides of O-benzyl-L-tyrosine.

Conformational studies of X[-L-Tyr(Bzl)-]n-series bound to polyethyleneglycol (X = H2, Nps; n = 3-8) in the solid state and in solvents of different polarities and capabilities of forming hydrogen bonds are reported. By using i.r. absorption, the occurrence of the beta-structure in the higher oligomers in the solid state was established. By means of i.r. absorption and CD the onset of that ordered conformation in solution was assessed as a function of chain length. The effects induced by the presence of the N-protecting group and added base, and by changing the nature of solvent on the conformational preferences of the [-L-Tyr(Bzl)-]n homo-peptides were also examined. The 2-nitrophenylsulphenyl chromophoric derivative of the alpha-amino group is proposed as a circular dichroism sensor for beta-structure in peptides.

Chemical Phenomena↗
PubMed1979

Protamines. III. Synthesis of the tetradecapeptide corresponding to the C-terminal sequence 52--65 of galline.

The synthesis of peptides containing blocks of arginyl residues is proposed through amidination of the corresponding ornithyl analogs. In order to test this strategy the ornithyl analog of the C-terminal sequence 52--65 of galline was synthesized by the conventional method. The amidination reaction, performed on fragments of different length and ornithyl-residue content, quantitatively converts ornithines into arginines. The strategy proposed may represent a powerful tool for the synthesis of protamines and other basic proteins.

Amidines↗
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

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↗