Biomedical subjects

G M Bonora

Publications and source records attributed to G M Bonora.

80 records · Page 5Linked to original sources

PubMedDate not supplied

Oligonucleotide conjugated to linear and branched high molecular weight polyethylene glycol as substrates for RNase H.

Two conjugates of an anti-HIV oligonucleotide (ODN) with different high molecular weight monomethoxy polyethylene glycols (MPEGs) have been tested for their activity as substrate towards RNase H. The MPEG does not impede the formation of the regular hybrid duplex with the target RNA sequence as pointed out by the persistence of the RNase H activity; thus, these derivatives stimulate the hydrolysis of RNA by the enzyme at the same site and with the same extent of cleavage as the native sequence.

Anti-HIV 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

(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

Synthesis and conformational analysis of (alpha Me)Leu/Aib model peptides.

We have synthesized by solution methods and fully characterized a variety of (alpha Me)Leu/Aib model peptides to the octapeptide level. A solution conformational analysis was performed by using infrared absorption. 1H nuclear magnetic resonance, and circular dichroism. The crystal-state structures of Z-D-(alpha Me)Leu-(Aib)2-OtBu, pBrBz-(Aib)2-D-(alpha Me)Leu-(Aib)2-OtBu, and Ac-(Aib)2-D-(alpha Me)Leu-(Aib)2-OtBu monohydrate were solved by x-ray diffraction. The results indicate that the (alpha Me)Leu residue may be easily incorporated into beta-bends and 3(10)-helical structures, and suggest that this residue tends to induce a helix handedness opposite to that promoted by its unmethylated counterpart (Leu) of the same optical configuration.

Aminoisobutyric Acids↗