At the institute, later
Rockefeller University, he worked as an Assistant for Dr.
D.W. Woolley on a dinucleotide growth factor he discovered in graduate school and on peptide growth factors that Woolley had discovered earlier. These studies led to the need for
peptide synthesis and, eventually, to the idea for solid phase peptide synthesis (SPPS) in 1959. In 1963, he was sole author of a classic paper in the
Journal of the American Chemical Society in which he reported a method he called "solid phase peptide synthesis". This article is the fifth most cited paper in the journal's history. In the mid-60s Dr. Merrifield's laboratory first synthesized bradykinin, angiotensin, desamino-oxytocin and insulin. In 1969, he and his colleague Bernd Gutte announced the first synthesis of the enzyme ribonuclease A. This work proved the chemical nature of enzymes.{{Citation |pmid = 17516587 |last=Jones |first=John H |publication-date=June 2007 Dr. Merrifield's method greatly stimulated progress in biochemistry, pharmacology and medicine, making possible the systematic exploration of the structural basis of the activities of enzymes, hormones and antibodies. The development and applications of the technique continued to occupy his laboratory, where he remained active at the bench until recently. In 1993,
Jeffrey I. Seeman published
Life during a Golden Age of Peptide Chemistry, Merrifield's autobiography, in the series "Profiles, Pathways, and Dreams" for the
American Chemical Society. He received the
Association of Biomolecular Resource Facilities Award for outstanding contributions to Biomolecular Technologies in 1998. The achievement of synthesizing
ribonuclease A (with Bernd Gutte) was all the more significant in that it demonstrated that the linear sequence of amino acids joined in
peptide bonds determined directly the
protein tertiary structure, that is, information coded in one dimension can directly determine the three-dimensional structure of a molecule. SPPS has been expanded to include solid phase synthesis of nucleotides and saccharides. ==Personal life==