Biomedical subjects

E Locardi

Publications and source records attributed to E Locardi.

5 recordsLinked to original sources

PubMed2001

Cyclic homooligomers from sugar amino acids: synthesis, conformational analysis, and significance.

Sugar amino acids (SAAs) were designed as new building blocks carrying an amino group and a carboxyl group on a carbohydrate scaffold. By exploiting standard solid- and solution-phase coupling procedures, linear and cyclic homooligomers containing glucosyluronic acid methylamine (Gum) were synthesized. We achieved a high yield and a very short coupling time for the oligomerization and cyclization of sequences encompassing two, three, four, and six Gum units. The synthesis of cyclic oligomers containing only SAAs as repetitive units has not been reported before. The conformational preferences in aqueous solution of the cyclic derivatives and their applications as potential host molecules are described herein. Benzoic acid and p-nitrophenol were chosen as model guest molecules to study the formation of cyclodextrin-like inclusion complexes. The complexation behavior of the cyclic hexamer was proved from three different points of view: chemical shifts, longitudinal relaxations (T(1)), and diffusion coefficients. All of them showed different values for host and guest molecules measured independently and in the presence of each other.

Amino Acids↗

PubMed1999

Conformations and pharmacophores of cyclic RGD containing peptides which selectively bind integrin alpha(v)beta3.

This paper reports a detailed conformational characterization in solution by 1H-NMR in H2O and DMSO-d6 and molecular modeling simulations of cyclic peptides containing the RGDDV pharmacophore and the RGDY(Me)R pharmacophore. These two pentapeptide sequences when properly constrained in cyclic peptides are low to sub-nanomolar inhibitors of integrin alpha(v)beta3. The peptides containing the RGDDY(Me)R sequence bind potently to integrin alphaIIb3 as well. The conformations found in H2O and in DMSO-d6 solutions are valuable for the design of peptidomimetics of these two pharmacophores. The structure-activity relationships of the RGDDV and RGDY(Me)R pharmacophores within cyclic peptides are discussed. Specifically, the orientation of surface-accessible chemical features on the ligand, such as hydrophobic, positive and negative ionizable groups, which are considered to be responsible for the desired biological activity, is focused on.

Magnetic Resonance Spectroscopy↗

PubMed1998

Collagen mimetics.

Collagen peptidomimetics have been synthesized as an alternative to natural collagen. The incorporation of unnatural residues such as peptoids in the collagen sequences can demonstrate potent and specific biological activity and enhance the biostability against enzymatic degradation. Furthermore, the use of achiral peptoids simplifies synthetic strategies by reducing racemization problems. The peptoid residue N-isobutylglycine (Nleu) has been successfully incorporated into a series of collagen mimetics composed of Gly-Pro-Nleu, Gly-Nleu-Pro, and Gly-Nleu-Nleu. The discovery of template-assembled collagen mimetics and metal binding ability has laid the foundation for new opportunities in the design of novel collagen mimetic complexes. The review summarizes the synthesis and integrated biophysical analyses of the structures of these collagen mimetics. Solid phase segment condensation techniques have been utilized for the synthesis of the single chain and template-assembled analogues. The characterization of the collagen-like structures has been established by temperature-dependent optical rotation measurements. CD, NMR spectroscopy, and molecular modelling simulations.

Circular Dichroism↗

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↗