Self-assembly is a spontaneous process by which unordered systems of monomers organize into ordered structures as the result of non-covalent interactions and lies behind a number of biological nanostructures. The concept of self-assembly has also been used in many disciplines for constructing useful materials. Supramolecular spontaneous assembly of high molecular weight peptides or peptides conjugated with non-peptidic molecules has been reported. Less is known on the self-assembly of short peptides alone which self-organize predominantly into nanotubes and nanofibers. Spherical (micellar and vesicle-like) architectures are rarely described although they appear very attractive, due to promising applications in biomedicine and nanotechnology.1 Besides the numerous advantages of using peptides containing natural amino acids for nanostructures, they present some limitations such as low bio-stability and unstable conformation especially when they are short or medium-sized. The insertion of unnatural amino acids in the peptide sequences is a well-known tool to overcome these problems.2 Here we report on the preparation and self-assembly of short hydrophobic peptides able to stabilize the formation of supramolecular spherical shape assemblies in water. Two diastereoisomeric pentapeptides AcAla-NRB-Ala-Aib-AlaNH2 1 and 2, containing the unnatural constrained norbornene amino acid (NRB) 3, were prepared. Interestingly, peptides 1 and 2 are insoluble in organic solvent but completely soluble in water despite the presence of hydrophobic non polar norbornene scaffold. The formation of a supramolecular assembly in water was assessed by DLS analyses for both 1 and 2 either as pure compounds or as a mixture. In all cases, the obtained assemblies showed almost monomodal distributions in the size range of 320-370 nm with low polidispersity. To assess their stability in conditions mimicking the in vivo environment, they were suspended in fetal bovine serum. Interestingly, peptide assemblies were found to keep their size and shape. An interesting feature of these peptides is also the presence of the C-C double bond in the norbornene scaffold, which could allow the easy labeling of the system introducing a variety of useful biotag. 1. Panda, J. J.; Chauhan, V. S. Polym. Chem. 2014, 5, 4418 2. Ruffoni, A. et al. RSC Adv., 2015, 5, 32643-32656

Spherical shape supramolecular structure of serum stable self- assembled pentapeptides containing the constrained norbornene amino acid / F. Clerici, M. Zuccolo, A. Ruffoni, M.V. Cavanna, S. Argentiere. ((Intervento presentato al 36. convegno Convegno della divisione di chimica organica tenutosi a Bologna nel 2015.

Spherical shape supramolecular structure of serum stable self- assembled pentapeptides containing the constrained norbornene amino acid

F. Clerici;M. Zuccolo;A. Ruffoni
Primo
;
2015-09

Abstract

Self-assembly is a spontaneous process by which unordered systems of monomers organize into ordered structures as the result of non-covalent interactions and lies behind a number of biological nanostructures. The concept of self-assembly has also been used in many disciplines for constructing useful materials. Supramolecular spontaneous assembly of high molecular weight peptides or peptides conjugated with non-peptidic molecules has been reported. Less is known on the self-assembly of short peptides alone which self-organize predominantly into nanotubes and nanofibers. Spherical (micellar and vesicle-like) architectures are rarely described although they appear very attractive, due to promising applications in biomedicine and nanotechnology.1 Besides the numerous advantages of using peptides containing natural amino acids for nanostructures, they present some limitations such as low bio-stability and unstable conformation especially when they are short or medium-sized. The insertion of unnatural amino acids in the peptide sequences is a well-known tool to overcome these problems.2 Here we report on the preparation and self-assembly of short hydrophobic peptides able to stabilize the formation of supramolecular spherical shape assemblies in water. Two diastereoisomeric pentapeptides AcAla-NRB-Ala-Aib-AlaNH2 1 and 2, containing the unnatural constrained norbornene amino acid (NRB) 3, were prepared. Interestingly, peptides 1 and 2 are insoluble in organic solvent but completely soluble in water despite the presence of hydrophobic non polar norbornene scaffold. The formation of a supramolecular assembly in water was assessed by DLS analyses for both 1 and 2 either as pure compounds or as a mixture. In all cases, the obtained assemblies showed almost monomodal distributions in the size range of 320-370 nm with low polidispersity. To assess their stability in conditions mimicking the in vivo environment, they were suspended in fetal bovine serum. Interestingly, peptide assemblies were found to keep their size and shape. An interesting feature of these peptides is also the presence of the C-C double bond in the norbornene scaffold, which could allow the easy labeling of the system introducing a variety of useful biotag. 1. Panda, J. J.; Chauhan, V. S. Polym. Chem. 2014, 5, 4418 2. Ruffoni, A. et al. RSC Adv., 2015, 5, 32643-32656
Settore CHIM/06 - Chimica Organica
Centro Interdisciplinare Materiali ed Interfacce Nanostrutturati - CIMAINA
Spherical shape supramolecular structure of serum stable self- assembled pentapeptides containing the constrained norbornene amino acid / F. Clerici, M. Zuccolo, A. Ruffoni, M.V. Cavanna, S. Argentiere. ((Intervento presentato al 36. convegno Convegno della divisione di chimica organica tenutosi a Bologna nel 2015.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/343709
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