Richard E. Mains

Richard E. Mains elucidated the biosynthetic pathways of neuropeptides derived from pro-opiomelanocortin, demonstrating how a single precursor protein generates multiple bioactive peptides through tissue-specific proteolytic processing. His characterization of the enzymatic machinery for peptide maturation established foundational understanding of neuropeptide production.

Working at the Johns Hopkins University School of Medicine, Mains studied how POMC is processed differently in anterior versus intermediate pituitary, yielding distinct peptide products: ACTH and β-lipotropin in corticotropes versus α-MSH and β-endorphin in melanotropes. These studies revealed that the same precursor generates different signaling molecules depending on cellular context, a paradigm that applies broadly across neuropeptide biology.

Mains collaborated with Betty Sue Eipper to characterize peptidylglycine α-amidating monooxygenase, the enzyme that converts glycine-extended peptide intermediates to their bioactive α-amidated forms. Their joint studies defined the structure, catalytic mechanism, and regulation of PAM, demonstrating its essential role in neuropeptide maturation. The partnership produced extensive characterization of prohormone convertases and other processing enzymes.

His research addressed how neurons regulate neuropeptide biosynthesis in response to physiological demands, showing that electroconvulsive treatment dramatically increases expression of PAM and prohormone convertases in hippocampal neurons. These findings connected peptide processing to neural plasticity and suggested regulatory control at the level of biosynthetic enzyme expression.

Mains and Eipper established the Neuropeptide Laboratory, which trained generations of scientists in peptide biochemistry. Their textbook chapter on neuropeptides in Basic Neurochemistry became a standard reference. At the University of Connecticut Health Center, Mains continued investigating neuropeptide biosynthesis while exploring roles of peptide-processing enzymes in development and disease.