Peptides and proteins have been known for more than a century, but was only when du Vigneaud published the
first synthesis of oxytocin, that the research on bioactive peptides was truly launched. Since then, the scientific progresses
in the field have been astonishing and the synthesis of peptides of virtually any size and complexity is now possible. Perhaps
the most important milestone was the development of the solid-phase peptide synthesis (SPPS) by Merrifield (1963),
to revolutionize the field. In this critic review, we will analyze how the SPPS contributed to widespread the manufacture
of peptides as active pharmaceuticals and what will be the challenges of tomorrow in this field.
Keywords: SPPS, LPPS, fmoc-chemistry, molecular machine, native chemical ligation.
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