Introduction

Abstract

The recognition by Hofmeister [1] and by Emil Fischer [2] that the structure of proteins is best represented by chains of amino-acids linked to each other through amide bonds, was preceded by the syntheses of the first simple peptide derivatives by Curtius [3] and later by Fischer [4]. The challenge that led to these endeavors can be discerned throughout the history of organic chemistry: reproduction or perhaps re-creation of the work of nature. Subsequently, the aims of peptide synthesis became more pragmatic. Preparation of small, well-defined peptides turned out to be indispensable for the study of the specificity of proteolytic enzymes. The synthetic peptides as substrates were models of complex proteins. In turn, the difficulties experienced in the synthesis of even such simple model compounds stimulated a sustained effort toward improvements in the methodology of peptide synthesis. With the discovery of biologically active peptides, the objectives of synthesis underwent a dramatic change. The isolation of oxytocin in pure form in Vincent du Vigneaud’s laboratory [5], the determination of its structure [6, 7] and, last but not least, its total synthesis [8] gave an unprecedented impetus to the development of synthetic procedures. The elucidation of the structure of insulin by Sanger and his associates [9] projected new and still higher aims for peptide synthesis: it should serve medicine in the study of peptide hormones and other peptides which play a role in the regulation of life processes. The classical role of organic chemistry to provide, through unequivocal synthesis, independent proof for the correctness of structures determined by degradation, remained one of the principal motivations in the development of peptide synthesis. Yet, it was also expected that the newly introduced procedures will be applicable for the practical production of peptides such as human insulin or important proteins, e.g. human growth hormone, crucially needed tools of medicine but scarcely available from natural sources. One has to admit, however, that over and above such rational reasons, synthesis of complex peptides was and still is attempted, like the climbing of mountains, because of the challenge of the endeavor.