Bodanszky M & du Vigneaud V. A method of synthesis of long peptide chains using a synthesis of oxytocin as an example. J. Amer. Chem. Soc. 81:5688-91, 1959

“Early in 1957 my wife, our five-year old daughter, and I arrived as refugees in New York City. I came to join du Vigneaud in his studies (recognized a year earlier by the Nobel Prize) on the chemistry of the peptide hormones oxytocin and vasopressin. Our newly acquired freedom, together with the absence of material possessions such as home, car, or television set, allowed me to concentrate on the task at hand: a new synthesis of oxytocin. At the same time, I was still somewhat obsessed by thoughts about my new procedure for the coupling of amino acids to each other, developed before I left Hungary: the nitrophenyl ester method.1 Thus, the idea to incorporate only protected-activated amino acids in the synthesis of oxytocin, rather than to follow the classical approach of combining segments of the peptide chain, presented itself quite naturally. The stepwise addition of single residues allowed systematic lengthening of the chain, without endangering the optical purity of the amino acid constituents Du Vigneaud enthusiastically approved the project and supported it with his tremendous knowledge of the problems surrounding oxytocin, his baby protein.’ The progress of the synthesis appeared breathtakingly fast. Within a short time we had a fairly large sample of oxytocin in our hand in a yield far exceeding the yields of The previously generally accepted method for the construction of peptides, combination of shorter segments of their chain, is replaced by a new approach to chain building, the addition of single amino acids. Unequivocal incorporation of the (protected) amino acids was achieved by the application of nitrophenyl esters. [The SCI® indicates that this paper has been cited over 615 times since 1961.]