Osvaldo Pieroni

Solution structure of dehydropeptides: A CD investigation

A CD investigation of eleven dehydropeptides is reported. The compounds investigated include tri-, tetra-, hepta-, and octapeptides and contain one, two, or three dehydro-phenylalanine (deltaPhe) residues. The peptides showed different CD profiles depending on chain length, position, and number of dehydro residues. The CD data very much complemented that provided by nmr studies, confirming the conformational preference for beta-bend structures in small peptides (tripeptides), and 3(10)-helical or alpha-helical structures in longer peptides. The secondary structures were stable in chloroform solution and were denatured by addition of trifluoroacetic acid. Solvent titration experiments performed by measuring CD as a function of solvent composition provided evidence that the order < or > disorder conformational changes occurred as cooperative transitions.

Light-induced conformational changes in chiral polymers with photochromic side chains

Preparation de polymeres optiquement actifs avec un squelette hydrocarbure et peptide portant des groupes photoisomerisables azobenzene et stilbene dans les chaines laterales par copolymerisation et par modification chimique de polymeres preformes. Etude du comportement photochrome et de la conformation en solution par absorption UV, fluorescence et dichroisme circulaire

Hepatotropic conjugate of adenine arabinoside monophosphate with lactosaminated poly-l-lysine: Synthesis of the carrier and pharmacological properties of the conjugate

BACKGROUND/AIMS The hepatotropic conjugate of adenine arabinoside monophosphate with lactosaminated poly-L-lysine (L-Poly(Lys)) must have a high solubility in order to be injected in a small volume compatible with the intramuscular route. In this paper the molecular weights of Poly(Lys) which allowed the synthesis of conjugates with the properties of high solubility and limited loss by the kidney were determined and a procedure for obtaining Poly(Lys) preparations with the required range of polymerization has been described. METHODS Conjugates were prepared using Poly(Lys) of different molecular weights obtained by the procedure described here or purchased from a commercial source. Their solubility and renal loss in mice was determined. RESULTS Poly(Lys) with molecular weights ranging from 45,000 and 65,000 Da guarantees high solubility and low renal elimination of the conjugates. Conjugate preparations with these properties, intramuscularly administered to woodchuck hepatitis virus-infected woodchucks for 37 days at a daily dose of 5.8 mg/kg exerted a strong antiviral activity. These preparations were devoid of acute toxicity in rat and caused no toxic effects when injected intramuscularly daily for 28 days at a dose ten times higher than that active in woodchucks. CONCLUSIONS The results support the possibility of a clinical use of L-Poly(Lys) to obtain liver targeting of adenine arabinoside monophosphate for the treatment of chronic hepatitis B virus infection.

New trends in photobiology: Synthetic photochromic polypeptides: possible models for photoregulation in biology

Abstract Naturally occurring photoreceptors usually contain low-molecular-weight photochromic molecules bound to a macromolecular matrix, such as a membrane protein. On irradiation, the photochromic moieties undergo reversible stereochemical rearrangements which, in turn, induce structural changes in the macromolecular matrix. This paper reports the behaviour of synthetic photochromic polypeptides which respond to light giving rise to reversible variations in their conformation, similar to photosensitive systems occurring in nature. Some examples are described in detail. Poly( l -glutamic acid) containing 20 mol.% azobenzene units in the side-chains adopts a random coil conformation in a micellar solution. Irradiation at 350 nm produces a coil → helix transition which is completely reversed by irradiation at 450 nm. In analogous conditions, azo-modified poly( l -lysine) undergoes a β-structureαα-helix transition. Poly( l -glutamic acid) containing spiropyran units adopts a random coil conformation in hexafluoro-2-propanol. Exposure to sunlight for a few seconds causes the spiralization of the polypeptide chains, which is completely reversed by dark adaptation. The mechanisms of the photoresponse effects are discussed and analogies with biological systems are indicated.

Photochromic poly(α-amino acid)s: photomodulation of molecular and supramolecular structure

Abstract Photochromic polymers are able to respond to light giving reversible variations of their structure and conformation which, in turn, are accompanied by variations of their physical and chemical properties. This paper describes the photochromic behaviour of poly(α-amino acid)s containing azobenzene and spiropyran groups in the side chains, and illustrates the most significative examples of their photoresponse effects. Experimental findings provide evidence that the molecular and supramolecular structure of these polypeptides can be photomodulated using the photosensitive side chains as effectors. The extent and the kind of photoresponse, including photoinduced coil ⇌ α-helix transitions, photostimulated aggregation/disaggregation processes, reversible variations of viscosity and solubility, were found to depend on polymer and environment conditions. Interpretative models of the photoresponse effects indicate that photochromic poly(α-amino acid) systems actually behave as amplifiers and transducers of the primary photochemical event occurring in the side chains, and therefore may be promising materials for application in optical technology.

Circular Dichroism of the Photoreceptor Pigment Oxyblepharismin

Abstract Circular dichroism (CD) was used to study the structure of oxyblepharismin (OxyBP), the photoreceptor chromophore for the photophobic response of the blue form of Blepharisma japonicum. Both the chromophore associated to its native protein and the free chromophore in ethanol solution were investigated. CD spectra in the far-UV range indicate that OxyBP induces a slight increase in the α-helix content of the protein matrix. CD spectra in the near-UV and visible region of the spectrum show that OxyBP adopts a chiral conformation with a preferential geometry not only when associated to its protein matrix, but also when isolated and dissolved in ethanol. This experimental result is related to the existence of a high-energy interconversion barrier between two enantiomeric structures of the molecule and discussed on the basis of an asymmetric biosynthesis of its precursor, blepharismin.

Photocontrol of the solubility of azobenzene-containing poly(L-glutamic acid)

The precipitation and dissolution of azobenzene-containing poly(L-glutamic acid) can be photoregulated by irradiation and dark adaptation, or by irradiating alternately at 338 and 450 nm.

Thermotropic photochromic polypeptides : Polyornithine and polylysine bearing azobenzene units in the side chains

Abstract The structure of poly(L-ornithine)s and poly(L-lysine)s containing between 19% and 100% of azobenzene units in the side chains has been studied, by X-ray diffraction, between room temperature and 250[ddot]C. Polymers were found to exhibit mesomorphic structures of the smectic A type deriving from the β-structure of polypeptides. The influence of the nature of the amino acid is discussed.

Spiropyran-containing poly(L-glutamic acid). Photochromic and conformational behaviour in acid conditions

Abstract Poly(L-glutamic acid) containing spiropyran groups in the side chains was found to exhibit reverse photochromism in hexafluoro-2-propanol in the presence of trifluoroacetic acid, but the polypeptide conformation was not affected by the photoisomerization of the photochromic units. When appropriate amounts of methanol were added as a cosolvent, the system responded to light giving reversible coil ← α-helix transitions whose extent depended on methanol concentration.

MODULATION OF THE RESPONSE OF POLYMER MATERIALS THROUGH MOLECULAR INTERACTIONS AND NANODISPERSION

Relevant examples are described here, concerning the light response of polypeptides bearing covalently bound photochromic groups in the side chains and the optical properties changes of nanocomposites from organic dyes aggregates dispersed in a thermoplastic matrix. The former system shows how the light induced structural changes in side chain chromophores can be amplified by the attached macromolecular response. The latter system provides evidence of the optical smart response to polymer/organic chromophores nanocomposite