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With the continous mission of the series to highlight research progress in peptide and protein science, this volume offers a state-of-the-art overview of contemporary areas including those that so far have had limited coverage. The volume reviewes literature predominantly published over the last two to three years providing revisions of background concepts that underpin emerging and developing technologies and methods. Being an integral part of each chapter, such an approach provides this series with a unique focus that while keeping pace with specific trends does not lose touch with the foundations.

The volume opens with a chapter describing advances in ligation techniques employed for the synthesis of peptides and proteins (Noisier and Albericio). As an alternative to the total chemical synthesis, ligation, and notably native chemical ligation, is being discussed from the perspective of developing a generic methogology to access a variety of protein and peptide targets, inlcuding glyco-proteins, that would not be limited to cysteine-mediated ligations as is in the native version. Different routes of using cysteine and thioester surrogates are assessed as more advanced and complementary approaches to existing methods. Ligation reactions are often reliant on spatially coordinated interplays of functional reactive groups, which hold important roles for large proteins and conformationally driven ligations. Similarly and related to this is the ability of certain amino acids and their combinations to coordinate metal binding, which can be allowed only by adopting specific geometries and topologies of and between polypeptide chains. This is the focus of a following chapter (Farkas and Sovago) which reviews the structural, equilibrium and kinetic aspects of metal-complex formations with a number of important applications, both analytical and synthetic. For the latter a particular emphasis is given to biologically important ligands which define contemporary approaches in metallopeptide chemistry and peptide design. Governed by the rational selection of specific amino-acid sequences ligand-protein interactions can be replicated in synthetic systems. Contributing to applications as broad as vaccination, molecular diagnostics and immunotherapies such systems can be structurally optimised while posing the need for new examples of naturally occuring protein recognition pairs. The next chapter (Uray and Hudecz) makes a comprehensive attempt to cover these and related aspects of peptide epitope selection. A main emphasis is made up on the structural optimisation of peptide epitopes ranging from sequential to conformational variants according to a traditional classification. Epitope mapping, particularly in the context of antibody-antigen recognition, using different recombinant constructs, microbial platforms and synthetic peptides as well as epitope manipulation based on conformationally constrained scaffolds and topographic mimetics are discussed in detail together with most relevant applications. A somewhat reverse approach, i.e. the optimisation of epitope-binding ligands, can be taken to design powerful inhibitors (enzymatic) that may hold promise as new efficient drugs. For example, aspartic protease inhibitors can serve as therapeutic candidates against hypertension, AIDS, leukaemia, malaria and Alzheimer's disease. Outlined in the next chapter (Hamada and Kiso), design approaches to such inhibitors include peptidic and non-peptidic constructs identified by screening chemical libraries, inhibitor-modulator combinations and sparingly soluble prodrugs based on click peptides addressing issues of drug selectivity and undesired side-effects. An application of higher order hierarchy in peptide scaffolding is explored in a following chapter (Oheix and Peacock), which discusses access routes to artificial metal-coordination, binding sites and selective co-factor mimetics (haem) through de novo protein design. Synthetic, structural and design strategies are outlined in detail with sufficient synergy allowing incorporating specialist biological applications while addressing pros and cons of creating non-native metal-binding sites. A common trend of folding-dependent structural and biological identity of peptides and proteins built throughout the chapters takes an ultimate form in the last chapter, which brings up a fundamental question of protein folding (Uversky and Uversky). In the spirit of this book series this closing review exposes the problem at all three structural levels – amino acids, peptides and proteins, positioning and developing its argument from the Levinthal's paradox, which implies a direct correlation between the length of an amino-acid sequence, the extent of information it stores and a precise folding pathway it encodes. As the discussion develops the apparent role of amino-acid sequences in defining protein form and function is determined allowing for a standpoint of an amino-acid code of protein folding, misfolding and non-folding.

In summary, all the chapters structured around their highlighted research areas set out from comparisons of existing concepts and approaches, each culminating with its own outlook of likely future develops and perspectives. The chapters are written by leading scientists in their respective research domains which enables a worldwide information source of broad appeal to academia and industry.

Etelka Farkas and Maxim Ryadnov

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