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C Pedone

Publications and source records attributed to C Pedone.

At least 91 records · Page 5Linked to original sources
PubMed1993

beta-Alanine containing peptides: gamma-turns in cyclotetrapeptides.

In the present paper we describe the synthesis, purification, single-crystal x-ray analysis, solution conformational characterization, and conformational energy calculations of the cyclic tetrapeptide cyclo-(beta-Ala-L-Pro-beta-Ala-L-Val). The peptide was synthesized by classical solution methods and the cyclization of the free tetrapeptide was accomplished in good yields in diluted methylene chloride solution using N,N-dicyclohexyl-carbodiimide. The compound crystallizes in the monoclinic space group P2(1) from ethanol with two independent molecules in the unit cell. All peptide bonds are trans. The nmr molecular conformation in the acetonitrile solution as well as that derived from the molecular dynamic simulation in vacuo is quite different from those observed in the solid state and is very similar to that previously observed for the parent compound cyclo- (beta-Ala-L-Pro-beta-Ala-L-Pro).

Amino Acid Sequence↗
PubMed1993

Noncoded residues as building blocks in the design of specific secondary structures: symmetrically disubstituted glycines and beta-alanine.

Structural changes can be induced in a peptide by selective substitution of coded alpha-amino acid residues by noncoded alpha-amino acid residues and the consequent production of analogues with modified structure and conformational preferences. In this review article we summarize the solid state structural results and the conformational preferences of two classes of "building blocks": (a) the linear and cyclic symmetrically alpha, alpha-disubstituted glycines in which either two identical n-alkyl groups replace the hydrogen atoms of the glycine residue or a cyclic aliphatic side-chain system is formed by linking the two alpha-carbon side chains, respectively; and (b) the beta-alanine residue. Examples, whenever possible, of the use of these residues for the elucidation of the bioactive conformation in the appropriate biological systems will be given.

Amino Acid Sequence↗
PubMed1993

Bioactive peptides: conformational study of a cystinyl cycloheptapeptide in its free and calcium complexed forms.

The disulphide bridged heptapeptide Boc-Cys-Val-Pro-Pro-Phe-Phe-Cys-OMe has been synthesized by classical solution methods. An ion binding study showed the peptide's ability to complex calcium ions with definite stoichiometry. The solution conformation of the peptide in its free and calcium-complexed form has been investigated by CD and nmr. The model structure derived from nmr data has been energy minimized and the resulting structure investigated by molecular dynamics simulation in water. The structure of the equimolar peptide/Ca2+ complex in acetonitrile at room temperature shows the presence of two transannular hydrogen bonds, with the formation of two ring structures of the C10 (type VIa) and C14 type. One peptide unit (Pro-Pro) is cis, all others are trans.

Acetonitriles↗
PubMed1993

Deletion mapping of the long arm of chromosome 10 in glioblastoma multiforme.

Cytogenetic and restriction fragment length polymorphism (RFLP) studies have shown that loss of one entire copy of chromosome 10 is a common genetic event in glioblastoma multiforme, the most malignant glial brain tumor in humans. In a search for submicroscopic deletions, we carried out an RFLP analysis using markers that had been mapped accurately on chromosome 10 by genetic linkage analysis. We studied 30 patients of whom 15 had loss of heterozygosity (LOH) at one or more loci. In seven cases, LOH was found at every informative locus, whereas in two cases extensive deletions were observed involving both the short and long arms. In six other patients, LOH was confined to a portion of the long arm. The smallest region of overlap among these latter six deletions was flanked by markers D10S12 proximally and D10S6 distally, a 33.4 centimorgan region that maps physically near the telomere (q25.1-qter). This region will serve as an important target for future mapping experiments designed to identify a tumor suppressor gene implicated in this lethal form of human cancer.

Chromosome Deletion↗
PubMed1993

Conformational versatility of the N alpha-acylated tripeptide amide tail of oxytocin. Synthesis and crystallographic characterization of three C2 alpha-backbone modified, conformationally restricted analogues.

The synthesis, physical and analytical characterization, and crystal-state structural analysis by X-ray diffraction of three analogues of the N alpha-acylated tripeptide amide tail of oxytocin, each containing a cyclic C alpha, alpha-disubstituted glycine at position 2, have been performed. The peptides are Boc-L-Pro-Ac3c-Gly-NH2, Z-L-Pro-Ac5c-Gly-NH2 and Z-L-Pro-Ac6c-Gly-NH2. While the former is folded in a type-II beta-turn conformation at the -L-Pro-Ac3c- sequence, the two latter tripeptides form two consecutive (type-II, type-I') beta-turns. The Ac5c- and Ac6c-tripeptides are the first examples of such a highly folded structural combination in a position-2 analogue of the N alpha-acylated -L-Pro-L-Leu-Gly-NH2 sequence.

Acylation↗
PubMed1993

Synthesis and neurokinin antagonist activity of 2-benzylidene- and 2-benzyl-3-benzylamino quinuclidines.

Molecular modeling studies based on the potent NK-1 antagonist CP-96,345 led us to the identification of some 2-benzylidene- and 2-benzyl-3-benzylaminoquinuclidine derivatives as potential antagonists at the NK receptor subtypes. The synthesized compounds, whose Z/E isomerism has been defined by X-ray analysis, show only moderate potency on the three neurokinin receptors. The possible reasons of the low potency exhibited by the tested compounds are discussed.

Amino Acid Sequence↗
PubMed1993

Non coded C alpha, alpha-disubstituted amino acids. X-ray diffraction analysis of a dipeptide containing (S)-alpha-methylserine.

The crystal and molecular structure of the fully protected dipeptide Boc-Val-(S)-alpha-MeSer-OMe has been determined by X-ray diffraction techniques. Crystals grown from ethyl acetate/n-pentane mixtures are tetragonal, space group I4(1), with cell parameters at 295 K of a = 15.307(2), c = 18.937(10)A, V = 4437.1A3, M.W. = 332.40, Z = 8, Dm = 0.99 g/cm3 and Dx = 0.995 g/cm3. The structure was solved by application of direct methods and refined to an R value of 0.028 for 1773 reflections with I > or = 3 sigma (I) collected on a CAD-4 diffractometer. Both chiral centers have the (S) configuration. The dipeptide assumes in the solid state an S shape. The urethane moiety is in the cis conformation, while the amide bond is in the common trans conformation. The conformational angles phi 1, psi 1 of the Val and phi 2, and psi 2 of the (S)-alpha MeSer fall in the F region of the phi-psi map. The isopropyl side chain of the Val residue has the (t, g-) conformation, while the Ser side chain has a g+ conformation. The hydrogen bond donor groups are all involved in intermolecular H-bond interactions. Along the quaternary axis the dipeptide molecules are linked to each other with the formation of infinite rows.

Crystallization↗
PubMed1992

Conformation for a beta-cyclodextrin monosubstituted with a cyclic dipeptide.

The structural characterization of a beta-cyclodextrin monosubstituted with the peptide cyclo(L-His-L-Leu) is reported. This work provides an x-ray example of a covalently bound group that folds in such a way that the terminal apolar side chain is retained in the hydrophobic interior of the cone-shaped cyclodextrin cavity. 6-Deoxy-6-cyclo(L-histidyl-L-leucyl)-beta-cyclodextrin crystallizes in the space group P1 with cell dimensions a = 14.728(8) A, b = 15.084(7) A, c = 18.182(10) A, alpha = 94.36(6) degrees, beta = 95.81(5) degrees, gamma = 116.08(9) degrees; overall isotropic agreement R = 10.6% for 5703 observed reflections (Fo greater than 3 sigma). The molecular structure consists of two independent molecules with the formula C54H86N4O36.7.25H2O. Each molecule assumes a "sleeping swan"-like overall shape with the hydrophobic leucine side chain inserted inside the cavity of the macrocycle. The two independent units give rise to a head-to-tail dimer linked by hydrogen bonds occurring between primary and secondary hydroxyl groups of the two monomers. The packing of the dimers produces cavities containing water molecules. There are infinite hydrophilic channels running in the crystal, which is similar to what is found in the structures of cyclic peptides.

Carbohydrate Conformation↗
PubMed1992

Beta-alanine containing peptides: a novel molecular tool for the design of gamma-turns.

In the present paper we describe the synthesis, purification, single crystal x-ray analysis, and solution conformational characterization of the cyclic tetrapeptide cyclo-(L-Pro-beta-Ala-L-Pro-beta-Ala). This peptide was synthesized by classical solution methods and the cyclization of the free tetrapeptide was accomplished in good yields in diluted methylene chloride solution using N,N-dicyclohexyl-carbodiimide (DCCI). The compound crystallizes in the orthorombic space group P2(1)2(1)2(1) from ethyl acetate. All peptide bonds are trans. The molecular conformation is stabilized by two intramolecular hydrogen bonds between the CO and NH groups of the two beta-alanine residues. These hydrogen bonds take place in a C7 structure in which both proline residues occupy the 2 position of an inverse gamma-turn. The two beta-alanine residues have a typical folded conformation (around the C alpha-C beta bond) observed in other cyclic peptides containing this residue. A detailed 1H-nmr analysis in CD3CN solution has been carried out. The molecule assumes a twofold symmetry in solution with a molecular conformation consistent with that observed in the solid state.

Amino Acid Sequence↗
PubMed1992

Characterization at atomic resolution of peptide helical structures.

A survey of literature for the various types of helices experimentally observed in high-resolution single crystal x-ray diffraction analyses of peptides has allowed to determine accurate conformational and helical parameters for the various secondary structures such as the alpha-helix, the 3(10)-helix, the fully extended conformation (2(5)-helix) and the beta-bend ribbon spiral. For each of these structures the characteristic phi, psi conformational parameters, n, the number of residues per turn, h, the height per residues and p, the pitch of the helix are described.

Models, Molecular↗
PubMed1992

Conformation of diastereomeric peptide sequences: structural analysis of Z-D-Val-Ac6c-Gly-L-Phe-OMe.

We have recently undertaken a systematic structural analysis of fully protected tetrapeptides containing at the N- and C-terminus either homo- or heterochiral amino acids, spaced by an achiral dipeptide segment. The interest for this class of peptides derives from the observation that, on reverse-phase (HPLC), the homo- and heterochiral sequences have a markedly different retention times. The diastereomeric sequences, namely Z-(L/D)-Val-X-Y-L-Phe-OMe (X = Sar, Gly, Ac3c, Aib, Ac5c, Ac6c, Deg, Dpg, Dbu, Dip, Dph; Y = Sar, Gly, Ac3c, Aib, Ac5c, Ac6c) show different overall hydrophobicity attributed to a different three-dimensional structure that also depends on the X-Y segment. Therefore, following preliminary studies in solution, we report here the detailed x-ray analysis of the tetrapeptide Z-D-Val-Ac6c-Gly-L-Phe-OMe in order to understand the structural features governing the overall hydrophobicity of linear fully protected tetrapeptides.

Amino Acid Sequence↗
PubMed1992

Molecular dynamics simulation in vacuo and in solution of [Aib5,6-D-Ala8] cyclolinopeptide A: a conformational and comparative study.

The conformation of a Cyclolinopeptide A analogue, c-(Pro-Pro-Phe-Phe-Aib-Aib-Ile-D-Ala-Val), has been investigated by means of molecular dynamics simulations, in various molecular environments. The molecular dynamics results are compared with that obtained for Cyclolinopeptide A and a detailed analysis of the different behaviour for the two compounds is reported. A complete analysis of hydrogen bonds is presented.

Amino Acid Sequence↗
PubMed1991

Ion binding of cyclolinopeptide A: an NMR and CD conformational study.

CD and nmr techniques have been used to study, in acetonitrile solution, the ion-complexing capability of cyclolinopeptide A (CLA), a cyclic nonapeptide of sequence cyclo-(Pro-Pro-Phe-Phe-Leu-Ile-Ile-Leu-Val) endowed with remarkable cytoprotective ability in vitro, and the conformation of the Ba(2+)/CLA complex. At room temperature, CLA in acetonitrile shows a proton nmr spectrum characteristic of the coexistence of many different conformers in intermediate exchange. The backbone contains a cis Pro-Pro bond, with all other peptide bonds in the trans conformation. CLA binds Ba2+ more tightly than the other cations studied, namely K+, Na+, Mg2+, and Ca2+; CD data are indicative of the presence of both 1:2 (sandwich) and 1:1 (equimolar) type complexes, depending on the Ba2+ ion concentration, whereas nmr data are consistent with an equimolar form. The relevant conformational features of the equimolar Ba2+/CLA complex are that the backbone contains all trans peptide bonds, a type I 6----3 beta-turn and a 3----1 gamma-turn (or a distorted 3----9 beta-turn). The global shape of the complexed peptide can be described as a bowl, with the concave (polar) side hosting Ba2+ and the convex side predominantly apolar.

Amino Acid Sequence↗
PubMed1991

beta-Alanyl-beta-alanine in cyclic beta-turned peptides.

In the present paper we describe the synthesis, purification, and single crystal x-ray analysis of the cyclic pentapeptide cyclo-(L-Pro-L-Pro-L-Phe-beta-Ala-beta-Ala). The peptide was synthesized by classical solution methods and the cyclization of the free pentapeptide was accomplished in good yields in diluted methylene-chloride solution using N,N-dicyclohexylcarbodiimide. The compound crystallizes in the monoclinic space group P21 from hot water with five solvent molecules. The Pro1-Pro2 peptide bond is cis and the molecular conformation is stabilized by an intramolecular hydrogen bond between the CO group of the beta-Ala5 and the NH of the Phe3 residue. The Pro1-Pro2 segment occupies the relative positions 2 and 3 of a type VIa beta-turn, while the L-phenylalanyl-beta-alanyl-beta-alanine segment is incorporated in a C13-like ring structure. The crystal packing is characterized by a network of 11 intermolecular hydrogen bonds involving all the remaining CO, NH, and the water molecules.

Crystallography↗
PubMed1991

Conformational study of cyclolinopeptide A. A distance geometry and molecular dynamics approach.

The conformation of cyclolinopeptide A, c(Pro-Pro-Phe-Phe-Leu-Ile-Ile-Leu-Val), a naturally occurring peptide with remarkable cytoprotective activity, has been investigated by means of distance geometry calculations and molecular dynamics simulations. The starting points for all the calculations were an X-ray structure and other structures obtained from distance geometry calculations based on NMR data. Restrained and unrestrained molecular dynamics simulations are reported in vacuo and in CCl4. Structural and dynamic properties are investigated and compared with those experimentally determined. The conformation obtained from the MD simulations which best reproduces the NMR parameters is at the same time one of the most stable ones and is also fairly similar to the crystal structure. An explanation for the occurrence of multiple conformations in solution at room temperature is given.

Amino Acid Sequence↗
PubMed1990

The longest, regular polypeptide 3(10) helix at atomic resolution.

A synthetic, terminally blocked homodecapeptide from the C alpha, alpha-dimethylated glycyl residue alpha-aminoisobutyric acid has been analyzed by single-crystal X-ray diffraction and the structure refined to R = 0.073. The compound crystallizes as a perfect 3(10) helix, stabilized by eight consecutive intramolecular N-H . . . O = C hydrogen bonds. This is the first observation at atomic resolution of a regular polypeptide 3(10) helix as long as three complete turns.

Aminoisobutyric Acids↗
PubMed1990

Stereochemical behavior of acyclic peptide-cation complexes.

The role of the beta-turns in the peptide interaction with several cations was investigated. In this work we report the solution studies of four linear peptides: Z-Aib-Aib-Aib-L-Val-OMe, Boc-D-aIle-L-Ile-D-aIle-L-Ile-OMe, Boc-L-Leu-L-Leu-L-Leu-L-Leu-OMe, and Boc-L-Phe-D-Phe-L-Phe-D-Phe-OMe. CD and 1H-nmr spectra reveal the presence of multiple ion-bonding equilibria. The stoichiometry and binding constant of the four peptides in the presence of Ca2+ ions in acetonitrile solution has been determined. Variable-temperature nmr spectra in the absence and in the presence of a large excess of cation have shown that the complexation process is not critically dependent on the conformation of the free peptide.

Amino Acid Sequence↗