Building peptides in liquid solution required painstaking, months-long crystallization after every single amino acid addition; Bruce Merrifield anchored growing peptide chains to insoluble plastic beads, allowing unreacted chemicals to be washed away in seconds. This ingenious solid-phase paradigm automated the chemical assembly of proteins and laid the foundation for modern peptide therapeutics like GLP-1 weight-loss drugs.

In the mid-twentieth century, medical researchers knew that short protein chains called peptides controlled human hormones and metabolism, but synthesizing even a tiny peptide in liquid flasks required a team of chemists working for an entire year. Every single amino acid addition required weeks of slow crystallization and suffered catastrophic yield loss.
Bruce Merrifield solved this with a brilliantly simple idea: tie the growing peptide chain to an insoluble microscopic plastic bead. The plastic bead acts like a secure molecular anchor, holding the protein in place while excess reagents are flushed down a drain with a quick wash, allowing automated assembly line manufacturing.
Solid-phase synthesis completely automated modern biotechnology. By slashing protein manufacturing from years to hours, by enabling the industrial production of life-saving insulin and modern GLP-1 medicines, and by paving the way for automated DNA synthesizers, Merrifield's bead method mechanized molecular medicine.
Solid Phase Peptide Synthesis. I. The Synthesis of a Tetrapeptide
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSolid Phase Peptide Synthesis. I. The Synthesis of a TetrapeptideR. B. MerrifieldCite this: J. Am. Chem. Soc. 1963, 85, 14, 2149–2154Publication Date (Print):July 1, 1963Publication History Published online1 May 2002Published inissue 1 July 1963https://doi.org/10.1021/ja00897a025Request reuse permissionsArticle Views34406Altmetric-Citations6225LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (944 KB) Get e-Alertsclose Get e-Alerts
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