Development of HIV fusion inhibitors.

In the past 25 years, the worldwide AIDS epidemic has grown such that roughly 38 million people were estimated to be living with the disease worldwide at the end of 2003. The introduction of antiretroviral-based therapies, beginning in 1987, has enabled many to live with HIV as a chronic, rather than terminal, disease. However, the emergence and spread of drug-resistant strains highlights the continued need for new therapies with novel modes of action.

Large-scale manufacture of peptide therapeutics by chemical synthesis.

The large-scale commercial production of a 36-amino-acid peptide by chemical synthesis has been demonstrated in the development of enfuvirtide (T-20 or Fuzeon), a first-in-class membrane fusion inhibitor for the treatment of HIV. The rationale behind route selection and the scale-up of the process used to manufacture enfuvirtide are discussed.