Amino Acids, Peptides and Proteins Volume 40 A Specialist Periodical Report Amino Acids, Peptides and Proteins Volume 40 Editors Maxim Ryadnov, National Physical Laboratory and University of Edinburgh, UK Ferenc Hudecz, Eo¨tvo¨s Lorand University, Budapest, Hungary Authors Szilvia Bo+sze, Eo¨tvo¨s L. University, Budapest, Hungary Marco Crisma, Institute of Biomolecular Chemistry, Padova Unit, CNR, Italy Gabriella Csik, Semmelweis University, Budapest, Hungary Emiliana De Santis, National Physical Laboratory, Teddington, UK Fernando Formaggio, Institute of Biomolecular Chemistry, Padova Unit, CNR, and University of Padova, Italy Takayuki Fukuda, Okayama University, Japan Ferenc Hudecz, Eo¨tvo¨s L. University, Budapest, Hungary Mizuki Kitamatsu, Okayama University, Japan Alicja Kluczyk, University of Wrocław, Poland A´da´m Orosz, Semmelweis University, Budapest, Hungary Maxim G. Ryadnov, National Physical Laboratory, Teddington, UK Hiromi Sasamoto, Okayama University, Japan Kohei Shingai, Okayama University, Japan Masahiko Sisido, Okayama University, Japan Piotr Stefanowicz, University of Wrocław, Poland Zbigniew Szewczuk, University of Wrocław, Poland Claudio Toniolo, Institute of Biomolecular Chemistry, Padova Unit, CNR, and University of Padova, Italy ISBN: 978-1-78262-059-4 eISBN: 978-1-78262-268-0 ISSN: 1361-5904 DOI: 10.1039/9781782622680 A catalogue record for this book is available from the British Library r The Royal Society of Chemistry 2016 All rights reserved Apart from fair dealing for the purposes of research for non-commercial purposes or for private study, criticism or review, as permitted under the Copyright, Designs and Patents Act 1988 and the Copyright and Related Rights Regulations 2003, this publication may not be reproduced, stored or transmitted, in any form or by any means, without the prior permission in writing of The Royal Society of Chemistry, or in the case of reproduction in accordance with the terms of licences issued by the Copyright Licensing Agency in the UK, or in accordance with the terms of the licences issued by the appropriate Reproduction Rights Organization outside the UK. Enquiries concerning reproduction outside the terms stated here should be sent to The Royal Society of Chemistry at the address printed on this page. Published by The Royal Society of Chemistry, Thomas Graham House, Science Park, Milton Road, Cambridge CB4 0WF, UK Registered Charity Number 207890 For further information see our web site at www.rsc.org Printed in the United Kingdom by CPI Group (UK) Ltd, Croydon, CR0 4YY, UK Preface DOI: 10.1039/9781782622680-FP005 Thisvolumecontinuesthemissionoftheseriesinprovidingasystematic and state-of-the-art overview of major research and development trends in peptide and protein science. Unlike many books and periodical re- views,thisseries,sinceitsinceptionbackin1969,aimstocoverdifferent areas of the field irrespective of their popularity or immediacy index in- cluding those that had limited coverage in recent years. Each volume reviews literature predominantly published over the last two–three years andoutlinesbackgroundconceptsthatunderpinfundamental,emerging and evolving disciplines and technologies. This approach is integral to each chapter in the series which grants each volume with a unique per- spectiveallowingthe monitoringofspecificadvancesindiscretesubject areas while keeping touch with foundations. This 40th volume opens with a chapter reviewing the essence of pep- tide and protein science – peptide bond formation (Crisma, Formaggio, Toniolo). The chapter is offered as a critical discussion that is built around reaction mechanisms in the context of reactivity and regiospe- cificity of peptide bond formation. Five major classes of C-component reactive derivatives of amino acids and peptides are cross-compared including fluorides, anhydrides, esters, azides and amides. The com- parisonisbasedon3DX-raystructuresofthederivativesandtacklesthe persistentissuesofchemicalandopticalhomogeneityofthereaction.Of direct relevance to the efficiency of peptide synthesis appears the prob- lemofdevelopingderivatizationreagentsforthequantitativeanalysisof post-translational modifications – capabilities that are increasingly nee- ded for modern ‘‘omics’’ approaches. This is the focus of a following chapter (Stefanowicz, Kluczyk, Szewczuk) which reviews the criticality of determiningamino-acidsequencestounderstandbiologicalprocessesat the molecular level. The chapter describes how mass spectrometry an- alysiscombinedwithchemicalmodificationshasbeenandisadvancing proteome research. A specific emphasis is made on soft ionization techniquesandtargetsforchemicaltaggingincludingexperimental and more traditional strategies. Derivatisation reagents are categorised in termsofprotonaffinity,charge,chemicalandenzymaticmethodsandin relation to target functional groups (thiols, amines, carboxyls). Pros and consoflabel-freemethods andisotopiclabellingarediscussedfrom the perspectiveofanalyticalreproducibilityandprecisionaswellasmethods applicablefordirectanalysisinbiologicalmedia.Astepforwardtowards the biotechnological developments of amino-acid labelling is taken in the next two chapters. In one (Sisido, Fukuda, Shingai, Kitamatsu, Sasamoto), a particular emphasis is placed on the application of fluor- escently labelled amino acids for screening cancer-cell binding peptides in situ and in vivo. The chapter describes different peptide screening protocols and compares their efficiency in in-solution and on-substrate formats. Experimental methodologies including higher order screening AminoAcids,Pept.Proteins,2016,40,v–vii | v (cid:2)c TheRoyalSocietyofChemistry2016 View Online and the solubility optimisation of selected sequences are given for de- tailed searches of peptide libraries and sub-libraries of short peptide unitsinavarietyofculturedcellsandinvivo.Anotherchapter(Oroszand Csik) instead looks into direct therapeutic effects of a new class of mo- lecular modalities, photosensitizers, which induce oxidative damages of cellular membranes and therefore hold promise in medicine. Usually referred to as photodynamic therapy, the strategy fully relies on photo- sensitiser conjugates with peptides and proteins and, by association, on the efficiency of the conjugation. The latter forms the bedrock of the discussion and highlights synthesis strategies, types of peptide carriers, from oligopeptide sensors and proteins to nanoscale conjugates, and their specific application targets. Photochemotherapy forms another substantial part of the discussion and focuses on antimicrobial and anticancer approaches including a contemporary reference to bioactive peptide sequences. The review of antimicrobial approaches takes an ul- timate turn in the next chapter which explains the impact peptides and proteins have on the treatment and diagnosis of M. tuberculosis in- fections(BoszeandHudecz).Hereadisease-centricfocusismatchedbya comprehensivecoverageoftheproblemwithaparticularattentiongiven tomethodologies andtools that enable thediscoveryofnewbiomarkers and peptide-based therapies. The challenges of epitope mapping, geno- micandinsilicomethodsaswellasinvitro,exvivoandinvivovalidation of identified epitopes and proteins are combined in one coherent dis- cussion. By acknowledging the nature of the bacterium the chapter guidesthereaderthroughkeydevelopmentsofimmunodiagnosticassays in accord with new epitope selections. M. tuberculosis peptidomes and proteomesareclassifiedaccordingtocellepitoperegions(Tcells,Bcells) while epitopes are presented in structural categories of linear peptides, conjugates, nanostructures and epitope-containing fusion proteins. The review culminates with applications including cell targeting, vaccine development and diagnostics. A specialist role of nanotechnology high- lightedthroughoutthisvolumecrystalisesinthelastchapter(DeSantis, Ryadnov) which explores inter-relationships between peptide sequence, folding and self-assembly for the construction of self-assembling motifs andtheirproducts–nanoscalematerials.Fourmajormaterialformsare described with each provided with established examples. As the dis- cussion develops the importance of commercialisation of peptide self- assembled materials becomes apparent and its near future prospects arereviewedincomparisontonon-peptidematerialsderivedfromother and somewhat more traditional molecular classes. A variety of appli- cations ranging from antimicrobials to nanoscale vectors for gene ther- apy and extracellular matrices for regenerative medicine closes up the volume. To sum up, each chapter is structured to give as contemporary a cov- erage as practical while allowing for comparisons of existing concepts and approaches. Each provides an outlook of likely future develops and perspectives as a part of discussion or summary. The chapters are written by leading scientists in their respective domains which ensures vi | AminoAcids,Pept.Proteins,2016,40,v–vii View Online expert-enabledaccesstoaworldwideinformationsourceofbroadappeal to research organisations and industry. We wish to dedicate this volume to the former co-editor of the seriesProfessorEtelkaFarkas(DebrecenUniversity,Hungary).Wethank her for all her diligent work to enable the resurrection of this series and for her outstanding contributions to maintain the high standard of the SPR. AminoAcids,Pept.Proteins,2016,40,v–vii | vii View Online CONTENTS Cover Nanoscaletopographic(AFM)and chemical(secondaryionmass spectrometry)imagesof antimicrobialporescreatedbyan antimicrobialpeptide,amhelin, inmimeticbacterialmembranes. ImagecourtesyofJean-Nicolas Audinot(CentredeRecherche PublicGabrielLippmann, Luxembourg). Preface v Insight into peptide bond formation from 3D-structural 1 chemistry Marco Crisma, Fernando Formaggio and Claudio Toniolo 1 Introduction 1 2 Carboxylic fluorides 2 3 Carboxylic anhydrides 4 4 Carboxylic esters 8 5 Carboxylic azides 24 6 Carboxylic amides 26 7 Summary and future perspectives 28 References 29 Derivatization of peptides for improved detection by mass 36 spectrometry Piotr Stefanowicz, Alicja Kluczyk and Zbigniew Szewczuk 1 Introduction 36 2 Targets for chemical tagging 39 3 Fixed charge chemical modifications of peptides and 40 proteins 4 Post-translational modifications 48 5 Tagging of peptides with isotopic labels 51 AminoAcids,Pept.Proteins,2016,40,ix–xi | ix (cid:2)c TheRoyalSocietyofChemistry2016 6 Studying derivatization: peptide modifications on solid 62 support 7 Conclusions and perspective remarks 68 Abbreviations 69 References 70 Fluorescently labelled amino acids and peptides for efficient 75 screening in situ and in vivo Masahiko Sisido, Takayuki Fukuda, Kohei Shingai, Mizuki Kitamatsu and Hiromi Sasamoto 1 Introduction 75 2 Fluorescent amino acids and multi-fluorophore 76 screening 3 In-solution peptide screening against intact proteins 81 4 In situ peptide screening against dish-cultured cells 82 5 In vivo peptide screening using multiple fluorophores 95 6 Conclusion 97 List of abbreviations 98 References 99 Peptide/protein conjugates of photosensitizers 100 A´da´m Orosz and Gabriella Csik 1 Introduction 100 2 Synthesis: strategies and approaches 102 3 Synthetic peptide carriers 107 4 Polypeptide and nano conjugates 119 5 Protein carriers 126 6 Outline, perspective 134 Abbreviations 136 References 137 Proteins and peptides for the immunodiagnosis and therapy of 146 Mycobacterium tuberculosis infections Szilvia Bo+sze and Ferenc Hudecz 1 Introduction 146 2 Identification of T cell epitope regions 148 3 Identification of B cell epitope regions 157 4 Epitope manipulation 165 5 Applications 180 6 Outline, perspective 185 Abbreviations 186 x | AminoAcids,Pept.Proteins,2016,40,ix–xi