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Biomedical subjects

G M Bonora

Publications and source records attributed to G M Bonora.

At least 37 records · Page 2Linked to original sources
PubMed1988

Long, chiral polypeptide 3(10)-helices at atomic resolution.

The crystal-state preferred conformation of the terminally blocked hepta- and octapeptides with the general formula -(Aib)n L-Leu-(Aib)2- (n = 4 and 5, respectively), determined by X-ray diffraction, was found to be a right-handed 3(10)-helix stabilized by five and six consecutive intramolecular NH...O = C H-bonds of the C(10)-III type, respectively. The octapeptide structure represents the first observation at atomic resolution of a regular, chiral 3(10)-helix larger than two complete turns. In both cases the right handed screw sense of the helix is dictated by the presence of the single, internal L-residue. This study confirms the propensity of short peptides rich in Aib, the prototype of the amino acid residues dialkylated at the alpha carbon, to adopt a 3(10)-helical structure and is expected to help our understanding of the conformational preferences of the membrane-active, channel-forming, ion-transporting peptaibol antibiotics.

Butyrates↗
PubMed1987

Conformational preferences and self-association modes of two diastereomeric statine derivatives.

The conformational preferences and self-association modes of the two diastereomeric N-acetyl, methylamides of 3-hydroxy, 4-amino, 6-methylheptanoic acid (statine) with (R, S) and (S, S) configurations at the 3-hydroxy and 4-amino carbons, respectively, have been determined in solution as well as in the solid state by infrared absorption, 1H nuclear magnetic resonance, and X-ray diffraction. Conformational energy computations have also been performed in parallel. In the crystal state, the change in chirality of the hydroxyl group induces different intermolecular H-bonding schemes in the (R, S) isomer compared to the two structurally distinct molecules in the asymmetric unit of the (S, S) isomer. Different propensities to self-aggregate are seen in solvents of low polarity. In solvents of high polarity, however, the molecules of both isomers are largely solvated, while still keeping some local conformational restriction. Conformational energy computations indicate that in vacuo the two diastereomers exhibit different flexibility, and a preferred conformation with a different type of intramolecular H-bond.

Amino Acids↗
PubMed1987

A search for new anti-herpes virus compounds.

This study reports on the synthesis and the activity of a series of new compounds of nucleoside-type structure. They are characterized for being differently substituted in the aromatic ring of the base (deazoadenosine derivatives) or by bearing a dansyl group in the sugar moiety (dansylthymidine). One molecule belonging to this latter class of compounds (the 3'-0-dansylthymidine) is showing an anti-herpesvirus potential while being active in inhibiting the virus-encoded enzyme thymidine kinase. This finding may represent an important step for the synthesis of new enzyme inhibitors and it is discussed in terms of future developments of more active congeners.

Adenosine↗
PubMed1987

Self-association and solubility of peptides. A solvent titration study of the 28-31 segment of corticotropin releasing factor.

Self-association of peptides related to the 28-31 sequence of corticotropin releasing factor in methylene chloride was disrupted by adding a variety of polar organic solvents in increasing amounts. This structural transition was monitored by the disappearance of either the amide-1 C = O stretching band (1635 cm-1) or the amide-A N-H stretching band (3300 cm-1) of strongly intermolecularly H-bonded molecules in the infrared absorption spectra. The effects induced by main-chain length, protection of the C-terminal group, nature of solvent, and peptide concentration were assessed. The increasing propensity to aggregate displayed by these peptides is paralleled by a decrease in their solubility.

Chemical Phenomena↗
PubMed1987

Structure, solubility and reactivity of peptides. A conformational study of two protected key intermediates from a large-scale synthesis of thymosin alpha 1.

A conformational study of two protected peptide segments, (1-10 and 11-28), spanning the entire sequence of thymosin alpha 1, in solvents of different polarity and capability of forming hydrogen bonds, is reported. By using infrared absorption and circular dichroism techniques the occurrence of the random coil conformation, the self-associated beta-structure, and the alpha-helix (the latter adopted only by the longer peptide) was established. The self-associated species of the two peptide segments were disrupted either by adding increasing amounts of hexamethylphosphoramide or by dilution. This structural transition was monitored by the disappearance of the amide-I C = O stretching band of strongly intermolecularly hydrogen-bonded molecules (near 1630 cm-1) in the infrared absorption spectra. The tendency of these peptides to aggregate is paralleled by a decrease in their solubility. The conformational findings are discussed in terms of the solvent-dependent product yields obtained in the reaction of segment (1-10) with the N alpha-deprotected (11-28) segment to give the fully protected thymosin alpha 1.

Circular Dichroism↗
PubMed1986

Retro-all-D and retro isomers of a formyl-methionyl peptide chemoattractant: an insight into the mode of binding at the receptor on rabbit neutrophils.

The retro-all-D analog and retro isomer of the formyl-methionyl-carboxamide-tripeptide chemoattractant, CHO-L-Met-L-Leu-L-Phe-NH2, namely CHO-D-Phe-D-Leu-D-Met-NH2 and CHO-L-Phe-L-Leu-L-Met-NH2, respectively, have been synthesized in solution by classical methods and fully characterized. The tetrapeptide CHO-L-Phe-Gly-L-Leu-L-Met-NH2, representing the C-terminal portion of the tachykinin, Substance P, and resembling the sequence of the retro isomer, has also been synthesized and characterized. The three N alpha-formylated tripeptide amides, prepared in order to obtain a deeper insight into the model of binding at the formyl peptide chemotactic receptor on rabbit neutrophils, have been tested for their ability to induce granule enzyme secretion from rabbit peritoneal neutrophils. The retro isomer, CHO-L-Phe-L-Leu-L-Met-NH2 is approximately 100-fold less active, the retro-all-D analog, CHO-D-Phe-D-Leu-D-Met-NH2 approximately 10,000-fold less active and the Substance P analog CHO-L-Phe-Gly-L-Leu-L-Met-NH2 1000-fold less active than the parent formyl peptide chemoattractant, CHO-L-Met-L-Leu-L-Phe-NH2. We interpret these results to indicate that a precise alignment of amino acid side chains as well as backbone amide bonds is an important factor involved in the receptor recognition of the formyl tripeptide chemoattractant.

Animals↗
PubMed1986

Nuclear magnetic resonance of protamines. A 1H-NMR study of the interaction of clupeine fractions with mononucleotides.

The interaction of the three clupeine fractions, YI, YII, Z, and salmine fraction AI with mononucleotides has been examined by means of 1H nuclear magnetic resonance. The results obtained are interpreted in terms of electrostatic interactions between positive arginine guanidinyl groups and negative nucleotide phosphates. In addition, clupeine fraction YI and salmine fraction AI exhibit with guanine and adenine nucleotides a more specific interaction that leads to the formation of large aggregates in solution. The experimental data presented in this work demonstrate that the strength of interaction between clupeine YI and salmine AI with mononucleotides follows the order: 5'-dTMP approximately equal to 5'-dCMP much less than 5'-dAMP less than 5'-dGMP approximately equal to 5'-GMP.

Adamantane↗
PubMed1986

Long polypeptide 3(10)-helices at atomic resolution.

The crystal-state preferred conformation of the terminally blocked homooctapeptide from the C(alpha,alpha)-dimethylated alpha-aminoisobutyric acid (Aib) residue, pBrBz-(Aib)(8)-OBu(t), in which pBrBz is para-bromobenzoyl and OBu(t) is tert-butoxy, determined by x-ray diffraction analysis using direct methods, was found to be a 3(10)-helix stabilized by six consecutive intramolecular N-H....O=C hydrogen bonds of the C(10)-III (or III') type. This is the first observation at atomic resolution of a regular 3(10)-helix longer than two complete turns. The solid-state structural analysis was extended to the terminally blocked, alpha-aminoisobutyric acid-rich octapeptide corresponding to the 2-9 sequence of the peptaibol antibiotics emerimicins III and IV, pBrBz-Aib(3)-L-Val-Gly-L-Leu-Aib(2)-OMe. Again, this peptide adopts a (right-handed) 3(10)-helical structure, although slightly distorted at the level of the L-leucine residue. The role of specific amino acid sequence and peptide main-chain length in stabilizing either the 3(10)- or the alpha-helical conformation and their possible implications on the nature of the channel formed by peptaibol antibiotics in the membrane are also briefly discussed.

Journal Article↗
PubMed1985

Molecular structure of peptaibol antibiotics: solution conformation and crystal structure of the octapeptide corresponding to the 2-9 sequence of emerimicins III and IV.

The infrared absorption and 1H nuclear magnetic resonance analyses of chloroform solutions of the terminally-blocked segment corresponding to the 2-9 sequence of emerimicins III and IV, -(Aib)3-L-Val-Gly-L-Leu-(Aib)2-, are consistent with the presence of a 3(10)-helical structure of high thermal stability. The crystal structure of the octapeptide, obtained by X-ray diffraction indicates the formation of a right-handed 3(10)-helix, stabilized by six consecutive intramolecular N-H....O:C H-bonds, slightly distorted at the level of the L-Leu residue.

Amino Acid Sequence↗
PubMed1985

Synthetic homo-oligomethionine chemoattractants. Conformation-activity study.

Using solution methods, we have synthesized several series of L-methionine homo-oligopeptides from the dipeptide to the hexapeptide with either a free alpha-carboxyl function or different C-blocking groups (methoxy, benzyloxy, benzylamino) and with N-blocking groups of either the amide type (formyl, pivaloyl) or the urethane type (tert.-butyloxycarbonyl). Compounds were compared to determine the combined effect of main-chain length and presence and nature of N- and C-blocking groups on conformation-activity relationship. Each peptide was tested for its ability to induce rabbit peritoneal polymorphonuclear leukocytes in the presence of cytochalasin B to secrete granule enzymes. In parallel, a conformational analysis was carried out in the solid state and in solution, using infrared absorption and circular dichroism. The biological and conformational data are discussed in relation to a recently proposed model of the chemotactic peptide receptor of rabbit neutrophils.

Animals↗
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↗
PubMed1984

Structural requirements for formyl homooligopeptide chemoattractants.

Using solution peptide synthesis, we have made three series of N alpha-formylated homooligopeptides, from the dipeptide to the heptapeptide, derived from L-methionine, L-norleucine, and S-methyl-L-cysteine and related to the chemotactic peptide N alpha-formylmethionylleucylphenylalanine. Compounds were prepared to determine the combined effects of the main-chain length and the presence of a sulfur atom in side-chain gamma- and delta-positions. Each peptide was tested for its ability to induce rabbit peritoneal polymorphonuclear leukocytes in the presence of cytochalasin B to secrete granule enzymes. In parallel, a conformational analysis was carried out in the solid state and in solution, using infrared absorption and circular dichroism. We examined these peptides in solvents of widely different polarities, i.e., chloroform, 2,2,2-trifluoroethanol, 1,1,1,3,3,3-hexafluoropropan-2-ol, and mixed organic-aqueous media. The tendencies to form antiparallel-chain beta-associated and folded structures were determined. The biological and conformational data are described in terms of a model of the chemotactic peptide receptor of rabbit neutrophils recently proposed by Freer et al. (1982) [Freer, R.J., Day, A.R., Muthukumarswamy, N., Pinon, D., Wu, A., Showell, H.J., & Becker, E.L. (1982) Biochemistry 21, 257-263]. In the three N alpha-formylated C-methoxy homooligopeptide series tested, the highest level of activity attained is at the tetrapeptide or pentapeptide stage, confirming the suggestion that the formylpeptide receptor is large enough to accommodate a peptide with at least four amino acid residues.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Chain-length dependence for secondary structure formation of homo-oligopeptides from epsilon-tert.-butyloxycarbonyl-L-lysine with a lipophilic C-terminal group.

A solid-state and solution analysis of the homo-oligopeptides from epsilon-tert.-butyloxycarbonyl-L-lysine with p-oxymethylbenzylcholestan-3 beta-yl succinate as C-terminal group, using infrared absorption and circular dichroism, is described. The occurrence of intermolecular beta-structure is seen in the solid state and in solvents of low polarity, e.g. methylene chloride, for peptides of intermediate size (from pentamer to decamer). Conversely, the eicosapeptide exhibits a high percentage of alpha-helical structure both in the solid state and in 2,2,2-trifluoroethanol. The influence of the C-terminal group on the conformational preferences of the epsilon-blocked homo-oligolysines in the solid state and in organic solvents appears negligible.

Chromatography, Thin Layer↗