Peptides in Paris.

Abstract

The Peptides in Paris Symposium – PIPS was held October 5-8, 2014, hosted at the University of Cergy-Pontoise and supported mainly by the Institute of Advanced Studies. The symposium was conceived to enhance dialogue between peptide scientists and to provide a novel forum for young researchers to learn more about the history and state-of-the-art technology of our growing field. The PIPS format featured a conference and poster session, tutorials, and a workshop with hands-on access to modern machines making impact in peptide science. This special issue highlights science discussed and inspired from the conference, which featured lectures from thirteen invited speakers, as well as established scientists and young investigators representing fourteen different countries. Notably, this issue is dedicated to leaders in the field, who presented tutorials at PIPS on seminal discoveries in their respective research areas: bioconjugates (Hudecz), cysteine-rich peptides (Moroder), conformational analysis (Toniolo), biophysical methods (Friedler), chemical ligation (Kent), post-translational modifications (Chorev), and peptide drug discovery and delivery (Danho). In the spirit of PIPS and in tribute to these leaders, this issue spans a variety of topics ranging from the synthesis and conformational analysis of peptides and peptidomimetics to their applications in various fields including chemical biology, immunology, materials science, biosensors, drug delivery and medicine. The PIPS special issue features sixteen original research articles and four review articles. Among the reviews, two focus on synthetic methods. Fernández-Llamazares et al. review peptide backbone N-modification, which has been employed to improve biological activity, optimize pharmacokinetic characteristics and to create peptide conjugates. Tapeinou et al. resume advances in the design and synthesis of cyclic peptides for drug discovery. Moreover, with attention on medicinal chemistry, Accardo et al. reviews drug delivery with peptide-targeted liposomes. In addition, to the study of peptides in materials science, Das et al. covers the application of single molecule force spectroscopy for studying molecular interactions between peptide structures and inorganic surfaces. Among the original research articles, two publications describe methods for peptide synthesis. A detailed mechanistic study by Chandra et al. probes their novel capping strategy that uses malonic acids as acylating agents. Ieronymaki et al. present a fundamental study by on solid-phase peptide synthesis using microwave chemistry on chlorotrityl resin. Various techniques are presented for probing peptides in biological systems. For example, by employing a peptide monolayer on a gold electrode Snir et al. report a sensitive electrochemical biosensor for measuring protein kinase activity. Through the synthesis and application of peptides embodying para-cyanophenylalanine as a fluorescence and infrared absorption probe, Bobone et al. report insight on the orientation of peptides that interact and make permeable membranes. Using 7-nitrobenz-2-oxa-1,3-diazole as a small molecule fluorescent probe, Swiecicki et al. have characterized influences of membrane lipid and peptide composition on cell penetration. By a computational approach featuring multivariate data analyses, Wynendaele et al. have categorized quorum-sensing peptides responsible for bacterial signaling leading to virulence and quiescence. The application of peptide structures for raising anti-bodies that may serve in diagnostics of infection and disease is described in two research articles. For example, to detect Staphylococcus aureus, Walczak et al. present a method for the generation of peptide-specific immunoglobulin Y (IgY) antibodies from egg yolks as an effective, economical alternative, which minimizes animal suffering. Real Fernández et al. illustrate the value of a library of linear and cyclic N-glucosylated peptide antigens to raise antibody probes for diagnosing multiple sclerosis and Rett syndrome. Pushing the boundaries of peptide science, Baskin et al. report on the synthesis and preliminary characterization of water-soluble metallopeptoids, one of which coordinates two metal ions in chiral distinct binding sites. In addition, Noichl et al. describe efforts towards the conception of intrinsically colored peptides through their investigation of methylated azatryptophan mutants of the Trp-cage mini protein. The PIPS issue provides a broad spectrum of developments in the application of novel synthetic amino acid and peptide analogs as peptidomimetics for controlling peptide conformation and developing biologically active analogs. For example, elaborating on the restraints provided by aminoisobutyric acid (Aib), Botz et al. report on the synthesis and incorporation of (R)-α-trifluoromethylalanine into short peptides that inhibit amyloid peptide fibrillation preventing Aβ aggregation. Ben Haj Salah et al. have employed 1,2,3-triazoles as isosteres of the Aib C-terminal amide in peptaibols to enhance metabolic stability and conformational rigidity. In the area of turn mimicry, X-ray structural analyses by Turcotte et al. illustrate that azasulfuryltripeptides can mimic γ-turns, and those of Doan, et al. show that N-amino-imidazolidin-2-ones can serve as β-turn mimics. Moreover, De Marco et al. employ 5-aminomethyloxazolidin-2,4-diones to synthesize integrin receptor antagonists. Finally, Romero-Estudillo et al. describe a site-selective means for modifying peptides by oxidative cleavage of amino acid residues bearing side chain hydroxyl groups in order to synthesize for example, novel α-aryl and α-alkyl glycine derivatives. In sum, this issue gives a healthy slice of the science presented and inspired by the PIPS meeting as it pays homage to the pioneers, who participated at the meeting. The scientific rapport, festive environment, and educational content of this meeting in Paris inspired enjoyable, productive and fruitful conversations and insightful discoveries. May this issue provide similar pleasure and inspiration for the readership to benefit from dissemination of some of the highlights from the Peptides in Paris Symposium. Anna Maria Papini Solange Lavielle William D. Lubell Co-editors and PIPS organizers Picture 1: Waleed Danho (University of Medicine and Dentistry of New Jersey, USA), Stephen Kent (Institute for Biophysical Dynamics, University of Chicago, USA), Ferenc Hudecz (Department of Organic Chemistry, Eötvös Loránd University, Budapest, Hungary), Chair Anna Maria Papini (University of Cergy-Pontoise, France), Co-chair Solange Lavielle (UPMC, Paris, France), Michael Chorev (Harvard Medical School, Cambridge, USA), Claudio Toniolo (University of Padova, Italy), Luis Moroder (Max Planck Institut für Biochemie, Martinsried, Germany), Co-chair William Lubell (Université de Montréal, Canada) Picture 2: PIPS 2014 Participants