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F Formaggio

Publications and source records attributed to F Formaggio.

At least 55 records · Page 3Linked to original sources
PubMed1998

Conformation and membrane activity of an analogue of the peptaibol antibiotic trichogin GA IV with a lipophilic amino acid at the N-terminus.

We have synthesized by solution-phase methods two analogues of the 11-residue lipopeptaibol antibiotic trichogin GA IV in which the N-terminal n-octanoyl group is replaced either by an N-acetylated 2-amino-2-methyl-L-undecanoic acid or by an N-acetylated alpha-aminoisobutyric acid. CD, FTIR absorption. and NMR analyses unequivocally show that the main structural features of trichogin GA IV are preserved in these analogues. Since only the peptide containing the lipophilic chain exhibits membrane-modifying properties, these results strongly support the view that moving the long acyl moiety from the Nalpha-blocking group to the side chain of the N-terminal extra-residue does not affect the conformational properties or the membrane activity of trichogin GA IV.

Amino Acid Sequence↗
PubMed1998

Solution conformational analysis of amphiphilic helical, synthetic analogs of the lipopeptaibol trichogin GA IV.

The step-by-step synthesis by solution methods of the [Ser2,5,6,9, Leu-OMe11] analog of trichogin GA IV is described. The four Ser residues have been incorporated into the sequence as replacements of the naturally occurring Gly residues to increase the amphiphilicity of the 3D-structure of the lipopeptaibol. A detailed solution conformational analysis has been performed on this undecapeptide and its prototypical [Leu-OMe11] trichogin GA IV analog using FTIR absorption and CD spectroscopies, and two-dimensional NMR under a variety of experimental conditions, including a membrane-mimetic environment. Both peptides adopt a mixed 3(10)/alpha-helical structure, which in the micellar system was found to be less flexible for the Ser-containing analog. For both analogs permeability measurements revealed membrane-modifying properties comparable to those of the natural lipopeptaibol.

Anti-Bacterial Agents↗
PubMed1996

Crystallographic structure of a multiple beta-turn containing, glycine-rich heptapeptide: a synthetic precursor of the lipopeptaibol antibiotic trichodecenin I.

In continuation of our studies on the structure and function of peptaibol antibiotics, the conformational properties of a sequence analogous to that of Trichodecenin I (Z-Gly-Gly-D-Leu-Aib-Gly-D-Ile-D-Leu-OMe, where Z = benzyloxycarbonyl, Aib = alpha-aminoisobutyric acid, and OMe = methyl ester) have been investigated crystallographically. This sequence is the mirror image of the naturally occurring molecule and also of the C-terminal heptapeptide of the related lipopeptaibol Trichogin A IV (where, however, the Leu-OMe residue has replaced the original Leuol residue). The molecule crystallized in the monoclinic system, space group P21, Z = 4, and cell parameters a = 11.610(5), b = 33.342(8), c = 11.735(4) A, beta = 110.42(1) degrees, V = 4257(3) A3. The crystallographic refinement converges at residual values of R = 0.047 and wR2 = 0.134 on F2. In the 1-5 segment the molecular conformation is virtually identical to that one reported from solution nmr studies of a similarly protected sequence [Biopolymers (1995), Vol. 35. pp. 21-29)] and is characterized by beta-turns of type I at Gly1-Gly2, II' at Leu3-Aib4, and I at Aib4-Gly5. In the crystal structure, a beta-sheet-like arrangement is seen at the C-terminus.

Anti-Bacterial Agents↗
PubMed1996

Structural versatility of peptides from C alpha, alpha-disubstituted glycines: crystal-state conformational analysis of peptides from C alpha-methylhomophenylalanine, (alpha Me) Hph.

The molecular and crystal structures of the C alpha-tetrasubstituted, delta-branched alpha-amino acid C alpha-methylhomophenylalanine, H-D-(alpha Me)Hph-OH, and three peptides (to the pentamer level), including the homotripeptide, have been determined by X-ray diffraction. The peptides are Z-L-(alpha Me)Hph-(L-Ala)2-OMe pBrBz-[D-(alpha Me)Hph]3-OtBu and Ac-(Aib)2-L-(alpha Me)Hph-(Aib)2-OtBu. All the (alpha Me)Hph residues prefer phi, psi torsion angles in the helical region of the conformational map. The two terminally blocked tripeptides adopt a beta-bend conformation stabilized by a 1<--4 C = O... H-N intramolecular H-bond. The terminally blocked pentapeptide is folded in a regular 3(10)-helix. In general, the relationship between (alpha Me)Hph alpha-carbon chirality and helix handedness is the same as that exhibited by protein amino acids. A comparison is also made with the conclusions extracted from published work on peptides from other types of C alpha-alkylated aromatic alpha-amino acids.

Aminobutyrates↗
PubMed1996

Crystallographic characterization of geometry and conformation of TOAC, a nitroxide spin-labelled C alpha,alpha-disubstituted glycine, in simple derivatives and model peptides.

The molecular and crystal structures of one derivative and two oligopeptides of TOAC, a nitroxide spin-labelled C alpha, alpha-disubstituted glycine, have been determined by X-ray diffraction. The derivative is the 5(4H)-oxazolone from Piv-TOAC-OH; the oligopeptides are Z-TOAC-(L-Ala)2-NHtBu sesquihydrate and pBrBz-TOAC-(L-Ala)2-TOAC-L-Ala-NHtBu hemihydrate. Incipient and fully developed right-handed 3(10)-helical conformations are formed by both independent molecules in the asymmetric unit of the terminally blocked tripeptide amide and the terminally blocked pentapeptide amide, respectively. The average geometry and preferred conformation for the piperidine ring of the TOAC residues are also discussed in detail.

Cyclic N-Oxides↗
PubMed1995

Characterization of beta-bend ribbon spiral forming peptides using electronic and vibrational CD.

Terminally blocked (L-Pro-Aib)n and Aib-(L-Pro-Aib)n sequential oligopeptides are known to form right-handed beta-bend ribbon spirals under a variety of experimental conditions. Here we describe the results of a complete CD and ir characterization of this subtype of 3(10)-helical structure. The electronic CD spectra were obtained in solvents of different polarity in the 260-180 nm region. The vibrational CD and Fourier transform ir (FTIR) spectra were measured in deuterochloroform solution in the amide I and amide II (1750-1500 cm-1) regions. The critical chain length for full development of the beta-bend ribbon spiral structure is found to be five to six residues. Spectral effects related to concentration-induced stabilization of the structures of the longer peptides were seen in the resolution-enhanced FTIR spectra. Comparison to previous studies of (Aib)n and (Pro)n oligomers indicate that the low frequency of the amide I mode is due to the interaction of secondary and tertiary amide bonds and not to a strong difference in conformation from a regular 3(10)-helix.

Amino Acid Sequence↗
PubMed1995

The polypeptide 3(10)-helix as a template for molecular recognition studies. Structural characterization of a side-chain functionalized octapeptide.

A N alpha-blocked, Aib-rich octapeptide methylamide containing two N omega-benzoylated L-Lys residues at positions 3 and 6 was synthesized by solution methods and fully characterized. A solution and crystal-state conformational analysis, performed by using FT-IR, 1H NMR, CD, and X-ray diffraction techniques, showed that the peptide is folded into a regular, right-handed 3(10)-helix stabilized by seven consecutive N-H...O=C intramolecular H-bonds of the beta-turn III type. The two benzamidobutyl L-Lys side chains, located on the same side of the helix after one complete turn, generate a cleft the minimal width of which was found to be 3.47 A.

Amino Acid Sequence↗
PubMed1995

The preferred solid-state conformation of (alpha Me)Trp peptides.

The two Z-L-Ala-DL-(alpha Me)Trp-NH2 diastereomeric dipeptides were synthesized from (Z-L-Ala)2(O) and H-DL-(alpha Me)Trp-NH2. The latter racemate, prepared by phase-transfer catalyzed alkylation of the N alpha-benzylidene derivative of alanine amide followed by acidic hydrolysis of the resulting Schiff base, was characterized by X-ray diffraction. The molecular and crystal structure of Z-L-Ala-L-(alpha Me)Trp-NH2, separated from its diastereomer by silica-gel column chromatography, was determined by X-ray diffraction analysis. Both independent molecules in the asymmetric unit of the dipeptide adopt a type-II beta-bend conformation. However, only the more regularly folded conformation of molecule B is stabilized by a 1<--4 C = O...H--N intramolecular H bond. The present results indicate that: (i) the C alpha-methylated (alpha Me)Trp residue is a strong beta-bend and helix former, and (ii) the relationship between (alpha Me)Trp chirality and helix screw sense tends to be opposite to that of protein amino acids. The implications for the use of the (alpha Me)Trp residue in designing conformationally restricted analogs of bioactive peptides are briefly discussed.

Amino Acid Sequence↗
PubMed1994

N alpha-benzyloxycarbonyl-alpha-aminoisobutyryl-glycyl-L-isoleucyl- L-leucine methyl ester monohydrate.

(Z)-Aib-Gly-L-Ile-L-Leu-OMe.H2O, C27H42N4O7.H2O, is a protected analogue of the C-terminal sequence of the membrane-active peptaibol antibiotic trichogin A IV. The peptide backbone is folded. The urethane carbonyl O atom acts as the acceptor of two intramolecular hydrogen bonds which give rise to a beta bend and to an alpha bend. The geometry of the latter is significantly distorted from that observed in alpha helices. This structure represents the first observation of an alpha bend in a protected tetrapeptide sequence.

Amino Acid Sequence↗
PubMed1994

Defect peptide chemistry: perturbations in the structure of a homopentapeptide induced by a guest residue interrupting side-chain regularity.

The fully blocked pentapeptide Tfa-(Deg)2-L-Abu-(Deg)2-OtBu (Tfa: triflouroacetyl; Deg: C alpha, alpha-diethylglycine; Otbu: tert-butoxy) adopts in the crystal state a regular, right-handed 3(10)-helical structure stabilized by three N--H...O=C intramolecular 1 < 4 (or C10) H bonds, as determined by an x-ray diffraction analysis. However, a Fourier transform ir absorption and 1H-nmr study strongly supports the view that in deuterochloroform solution the four Deg residues at both termini of the peptide main chain are involved in successive, fully extended C5 forms. A comparison with the stable, fully developed, multiple C5 conformation of Tfa-(Deg)5-OtBu indicates that incorporation of an Abu guest residue, interrupting the side-chain uniformity of the host (Deg)5 homopeptide, while altering only marginally the conformation in a solvent of low polarity, is responsible for a dramatic perturbation of the crystal-state structure.

Amino Acid Sequence↗
PubMed1994

Onset of the fully extended conformation in (alpha Me)Leu derivatives and short peptides.

The X-ray diffraction crystal structures of the (alpha Me)Leu derivative mClAc-D-(alpha Me) Leu-OH and the terminally protected tripeptide Z-D-(alpha Me) Leu-(L-Ala)2-OMe show the onset of the fully extended (C5) conformation for the (alpha Me) Leu residue in both independent molecules in the asymmetric unit of the former compound and in two out of the four independent molecules in the asymmetric unit of the latter compound. In addition, conformational analysis in CDCl3 solution (using FT-infra-red absorption and 1H nuclear magnetic resonance) revealed the occurrence of a significant population of fully extended conformers throughout the entire sequence of the (alpha Me) Leu homochiral homopeptides pBrBz-[D-(alpha Me) Leu]n-OtBu (from monomer to tetramer). Taken together, these results represent a clear indication that this peptide secondary structure, uncommon for protein amino acids and other C alpha-methylated chiral residues, is not a rare observation in (alpha Me) Leu derivatives and short peptides.

Amino Acid Sequence↗
PubMed1994

Structure determination of racemic trichogin A IV using centrosymmetric crystals.

Direct methods of crystal structure solution are greatly facilitated in centrosymmetric space groups where the complexity of the phase-problem is reduced. For most peptides and proteins, crystallization in a centrosymmetric arrangement is precluded by an intrinsic dissymmetry due to the constituent chiral amino acid residues. The synthetic accessibility of peptide sequences containing amino acids of either chirality offers the possibility for co-crystallization of racemic crystals. We report here the first use of such an approach for the de novo structure determination of a medium-sized molecule, trichogin A IV, which is a constituent of a fungal lipopeptaibol mixture possessing membrane-modifying properties of biological interest.

Amino Acid Sequence↗
PubMed1993

Structures of peptides from alpha-amino acids methylated at the alpha-carbon.

The structural preferences of peptides (and depsipeptides) from the achiral MeAib and Hib residues, and the chiral Iva, (alpha Me) Val, (alpha Me) Leu, and (alpha Me) Phe residues, as determined by conformational energy computations, x-ray diffraction analyses, and 1H-nmr and spectroscopic studies, are reviewed and compared with literature data on Aib-containing peptides. The results obtained indicate that helical structures are preferentially adopted by peptides rich in these alpha-amino acids methylated at the alpha-carbon. Intriguing experimental findings on the impact of the chirality of Iva, (alpha Me) Val, and (alpha Me) Phe residues on helix screw sense are illustrated.

Amino Acid Sequence↗
PubMed1993

Reverse relationship between alpha-carbon chirality and helix handedness in (alpha Me)Phe peptides.

The crystal-state preferred conformations of two tripeptides, one tetrapeptide, and one pentapeptide, each containing a single residue of the chiral, C alpha, alpha-disubstituted glycine C alpha-methyl, C alpha-benzylglycine [(alpha Me)Phe], have been determined by X-ray diffraction. The tripeptides are Z-L-(alpha Me)Phe-(Aib)2-OH dihydrate and Z-Aib-D-(alpha Me)Phe-Aib-OtBu, the tetrapeptide is Z-(Aib)2-D-(alpha Me)Phe-Aib-OtBu, and the pentapeptide is pBrBz-(Aib)2-DL-(alpha Me)Phe-(Aib)2-OtBu. While the two tripeptides are folded in a beta-bend conformation, two such conformations are consecutively formed by the tetrapeptide. The pentapeptide adopts a regular 3(10)-helix promoted by three consecutive beta-bends. This study confirms the strong propensity of short peptides containing C alpha-methylated alpha-aminoacids to fold into beta-bends and 3(10)-helical structures. Since Aib is achiral, the handedness of the observed bends and helices is dictated by the presence of the (alpha Me)Phe residue. In general, we have found that the relationship between (alpha Me)Phe chirality and helix handedness is opposite to that exhibited by protein aminoacids. A comparison with the preferred conformation of other extensively investigated C alpha-methylated aminoacids is made.

Models, Molecular↗
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↗