Peptides are key to modern drug discovery. This article reviews the requirements for bulk production of peptides and how it affects research and production of smaller scales. Peptides, as modern drugs, are currently produced in millions in mg-scale for research purpose, in order to better understand the function of biological systems. Some newly discovered sequences form the basis of modern drugs and are now produced in multi-tons. The most popular example is the T-20 peptide (Fuzeon), which is the first peptide produced at such scale by a combination of solid phase and solution phase methodologies. This particular peptide sequence has the ability to dock on the surface of the HIV virus and block the virus from entering into a human blood cell, helping patient life conditions. A multi-ton scale production was made necessary based on the high number of patients, the socio-economical importance of the disease and the strong support by governmental institutions such as the FDA. Fuzeon is the first peptide-based drug that is produced in multi-tons on solid support. This had revolutionary effects on the whole peptide synthesis techniques in general including the production of the starting materials. It also had a positive impact on the cost-effectiveness of peptides for research, as the standard technique for producing peptides in research quantities is solid phase chemistry. The decrease of the cost of all starting materials will lead to an increase of the number of produced peptides, which will certainly bring new interesting and effective sequences to be used as novel drugs.

Enzyme-labile protecting groups have emerged as a green alternative to conventional protecting groups. These groups introduce a further orthogonal dimension and eco-friendliness into protection schemes for the synthesis of complex polyfunctional organic molecules. S-Phacm, a Cys-protecting group, can be easily removed by the action of a covalently immobilized PGA enzyme under very mild conditions. Herein, the versatility and reliability of an eco-friendly combination of the immobilized PGA enzyme and the S-Phacm protecting group has been evaluated for the synthesis of diverse Cys-containing peptides.

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An easy and efficient solid-phase synthesis strategy to obtain rapidly water-soluble chromophores/fluorophores in highly pure form has been developed. This first successful use of N-Fmoc-α-sulfo-β-alanine as a SPPS building block opens the way to the future development of promising direct "on-resin" peptide labelling and water-solubilising methods.

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