Bruce Merrifield and solid‐phase peptide synthesis: A historical assessment

Abstract

Bruce Merrifield, trained as a biochemist, had to address three major challenges related to the development and acceptance of solid‐phase peptide synthesis (SPPS). The challenges were (1) to reduce the concept of peptide synthesis on a insoluble support to practice, (2) overcome the resistance of synthetic chemists to this novel approach, and (3) establish that a biochemist had the scientific credentials to effect the proposed revolutionary change in chemical synthesis. How these challenges were met is discussed in this article. © 2008 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 90: 175–184, 2008.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

The Formation and Self‐Assembly of Long Prebiotic Oligomers Produced by the Condensation of Unactivated Amino Acids on Oxide Surfaces

“…[3] Furthermore, the catalytic formation of long polypeptides from unactivated amino acids could be of interest for new synthetic strategies aimed at avoiding poor atom economy reagents, in addition to well-established solid-phase peptide synthesis methods. [6] In a previous study, we revealed the role of the (101) and (001) facets of anatase TiO 2 nanoparticles in activating adsorbed carboxylate moieties toward a nucleophilic attack of amines to form amides. [7] In the present study, we extend the investigation to the adsorption of glycine (Gly) vapors (with molecules in the nonionic HOOC-CH 2 -NH 2 form) by adopting the experimental procedure established for adsorbing Gly onto hydroxyapatite (HA) nanoparticles.…”

Applications of Enzymes in Synthesis and Modification of Polymers

“…A terceira abordagem envolve o uso de enzimas que não sejam esterases ou proteases, e será exemplificada mais a seguir nesta seção. 66 As proteases são classificadas em 6 grupos, com base em seus sítios ativos (note-se que existem outras formas de classificação de proteases, como a que se baseia em sua forma de atuação sobre o substrato -endopeptidases, exopeptidases, etc): serina proteases (como a tripsina, quimiotripsina e subtilisina), 67 treonina proteases, 68 cisteína proteases (como a papaina e a bromelina), 69 aspartato protease (como a pepsina), 70 glutamato protease 71 e metaloprotease (como a termolisina). 72 A síntese de polipeptídeos catalisada por proteases pode ocorrer regida por um controle termodinâmico ou cinético.…”

Electrophile Cleavable Linker Units

“…Bruce Merrifield was the first to recognize the usefulness of polymer-supported organic synthesis, and is best known for the invention and development of solid-phase peptide synthesis (SPPS), which revolutionized synthetic organic chemistry. [29] Merrifield planned to attach the C-terminal amino acid to an insoluble particle throughout the synthesis and to grow the peptide chain on that residue. [30] His first successful synthesis by SPPS was of the tetrapeptide, L-Leu-L-Ala-L-Gly-L-Val on nitrochloromethylphenyl polymer resin using benzyloxycarbonyl (Cbz)-protected amino acids (30% hydrogen bromide in acetic acid for the deprotection, N ,N -Dicyclohexylcarbodiimide (DCC) in DMF for the peptide-forming step, 2 N sodium hydroxide in ethanol for the peptide liberation step).…”