1 Full Paper Macromolecular Chemistry and Physics wileyonlinelibrary.com © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim DOI: 10.1002/macp.201400471 Bioinspired Nanotubes from Self-Assembly of a Linear L, D-Oligopeptide-Poly(ethylene glycol) Conjugate Pasqualina Punzi, Serena De Santis, Cesare Giordano, Marco Diociaiuti, Federica Novelli, Giancarlo Masci, Anita Scipioni* The preparation and structural organization of a new bioinspired nanomaterial are investi- gated. A hybrid conjugate is obtained by end-linking a linear octapeptide with regular alter- nating enantiomeric sequence to poly(ethylene glycol). This conjugate is able to self-assemble, forming well-defined nanorods having core/shell morphology with an internal peptide single channel that has, for the first time, been clearly visualized by transmission electron micros- copy (TEM) images. It is remarkable that well-defined cylin- drical nanoparticles can be formed starting from a linear oligopeptide, the synthesis of which is significantly easier than that of the homologous cycles. In addition, the synthetic strategy and the structure of the conjugate ensure a con- trolled and regular pegylation of the aggregates and high den- sity PEG blocks in the corona, making the nanoparticles more resistant to phagocytosis and able to prevent biofouling. Such features, along with biocompatibility and stability, make these nanoparticles promising candidates for drug delivery. Dr. P. Punzi, Dr. S. De Santis, Dr. F. Novelli, Dr. G. Masci, Dr. A. Scipioni Dipartimento di Chimica, Università La Sapienza, Piazzale A. Moro, 5, I-00185 Rome, Italy E-mail: anita.scipioni@uniroma1.it Dr. C. Giordano Istituto di Chimica Biomolecolare, CNR, Università La Sapienza, Piazzale A. Moro, 5, I-00185 Rome, Italy Dr. M. Diociaiuti Dipartimento di Tecnologie e Salute, ISS, Viale Regina Elena 299, I-00161 Rome, Italy Dr. A. Scipioni Istituto Pasteur, Fondazione Cenci-Bolognetti, Viale Regina Elena 291, I-00161 Rome, Italy and nanomedicine. [1] Contemporarily, self-assembly is emerging as a powerful bottom-up approach for their prep- aration. By designing small molecules that self-assemble into large structures, it is possible to control over the func- tionality as well as the architecture of the final material. [2] In the last two decades, much interest has been addressed toward oligopeptides as building blocks for biologically inspired architectures with manifold applica- tions. Self-assembling peptide-based nanotubes are among bioactive compounds widely investigated for the develop- ment of novel biomaterials. [3–6] Sequential condensation of proper amino acids provides an easy route for the synthesis of oligo- and polypeptides. Furthermore, the chemical ver- satility of their side chains allows various chemical modifi- cations with the purpose of adding new functionalities for their possible use in pharmacology and nanotechnology. Among the strategies developed for peptide nanotube engineering, those characterized by regularly alternating enantiomeric sequences are particularly attractive. 1. Introduction Nanomaterials with well-defined structures and func- tions have come to be important in a wide range of fields, from microelectronics and sensors, to catalysis Early View Publication; these are NOT the final page numbers, use DOI for citation !! Macromol. Chem. Phys. 2014, DOI: 10.1002/macp.201400471