Preface

Amino acids, peptides and proteins is a book series that was launched in 1969 to provide a systemic overview of modern research in peptide and protein science. Since its inception the series has been covering different topics within the field without being biased by the pressures of popularity or fashion. This has helped to keep abreast with achievements in seemingly less popular areas having a limited coverage in the mainstream literature. Understandably, as any other series of the type these periodical reports have evolved into research accounts with an increasingly broader coverage at the expense of new and emerging research areas. This volume is of no exception and continues the tradition of bringing new and established science together. The book reviewes literature predominantly published over the last three years, with each chapter striving to give a unique perspective, while providing sufficient background information to help the reader with fundamental concepts and terminology.

The 41st volume opens with a critical review of current developments in the design and synthesis of anti-HIV agents derived from peptides (Ohashi and Tamamura). The review starts with more conventional strategies relying on enzyme inhibitors of reverse transcriptases, proteases and integrases as well as on their use in combined therapies. It then tackles the issue of developing robust approaches involving other and broader targets that can be engaged with mid-sized peptide derivatives serving as fusion inhibitors, co-receptor antagonists, CD4 mimetics and vaccines. The next chapter takes over with equally important aspects of handling the causes of diseases highlighting progress in biomarker discovery (Nice). An emphasis is placed on enabling technologies, experimental and computational, that can accelerate the uptake of new applications. Both therapy and diagnostics use protein labelling to inform next steps in drug development. Labelled peptides and proteins offer molecular reporters that are traced and measured by specialist detection methods. This is the subject of a following chapter (Antonatou, Gunnoo, Vannecke, Madder), which extends the discussion into pros and cons of cross-linked ligand–protein and protein–protein complexes in the formulation of biologics. While covalent cross-linking provides an effecitve means for functional bioconjugation, proteins are even more effective in the formation of non-covalent functional complexes to deliver various bioactivities. One class of such strategies, metal complexation, is presented in an updated overview on metal complexation by amino acids, peptides and related compounds (Farkas and Savago). This next chapter discusses the role of formed and forming complexes for applications in medicinal chemistry. Apart from classical kinetic and structural questions, sequence-specific complexation is scoped within cysteinyl and histidyl residues implicated in biologically relevant ligand binding. A logical progression of the paper is given in a following chapter (Szöllősi, Chiba, Szakács, Stockner, Hegedűs) introducing the problem of drug transport mediated by ATP-binding cassette proteins (ABC). This review offers an assessment of how the elucidation of protein structure, in general and exemplified by the family of human multidrug ABC transporters, can advance computational tools to allow the prediction of substrate recognition and protein translocation mechanisms. To this point, all the chapters refer to the problem of cooperative and stimuli-dependent folding, whether it is metal binding or ligand–protein interactions. The subject is fundamental for protein science, while conformational changes in individual proteins may be deemed unique. In this regard, naturally derived and artificial peptides are being viewed as suitable sources for model systems that can help build up consistent hierarchical relationships between protein structure and function. To probe such systems requires measurement capabilities that can handle native and near-native environments (i.e. water, lipid membranes, extracellular milieu) and which can differentiate the impact different substrates may have on protein behavior. These issues are discussed in the last two chapters that, respectively, describe the biophysical modulation of peptide–lipid interactions (Ravi and Ryadnov) and the surface and interface analysis of functional proteins and peptides (Fearn and Ray), with both reviews giving recent examples of biologically relevant case studies.