Arthur M. Felix
Arthur M. Felix advanced solid-phase peptide synthesis through methodological innovations that improved coupling efficiency, cyclization strategies, and peptide modification for therapeutic applications. His work at Hoffmann-La Roche established practical solutions to longstanding synthetic challenges while pioneering site-specific PEGylation of peptides.
Felix received his Ph.D. from Brooklyn Polytechnic Institute and joined Hoffmann-La Roche, where he led the Peptide Research Department for decades. His group developed the use of the BOP reagent for difficult couplings, demonstrating that this phosphonium-based activator outperformed traditional carbodiimide methods for sterically hindered sequences. They optimized on-resin cyclization procedures, achieving side-chain to side-chain lactam formation within two hours using BOP activation.
His multidisciplinary research program addressed growth hormone-releasing factor analogs through rational design informed by conformational analysis. Felix developed cyclic GRF analogs with enhanced stability and potency, demonstrating that constrained peptides could maintain helical structure in aqueous solution while resisting proteolytic degradation. His group pioneered site-specific PEGylation strategies for synthetic peptides, establishing methods for N-terminal, internal, and C-terminal modification that extended biological half-lives and improved pharmacokinetics.
Felix introduced fluorescamine as a terminating agent for blocking unreacted amino groups during synthesis and developed a fluorescence-based monitoring alternative to the classical ninhydrin test. His investigations into the biophysical basis of difficult couplings provided mechanistic understanding that informed practical solutions. A founder of the American Peptide Society in 1990, Felix served in leadership roles and later produced, with Bruce Merrifield and colleagues, the 2001 documentary Peptide and Protein Synthesis: Origin and Development. After retiring from Roche, he taught at William Paterson University and Ramapo College of New Jersey until 2012.
