Rational Design of an Organocatalyst for Peptide Bond Formation

Handoko, Sakilam Satishkumar, Nihar R. Panigrahi, Paramjit S. Arora

Research output: Contribution to journalArticle

Abstract

Amide bonds are ubiquitous in peptides, proteins, pharmaceuticals, and polymers. The formation of amide bonds is a straightforward process: amide bonds can be synthesized with relative ease because of the availability of efficient coupling agents. However, there is a substantive need for methods that do not require excess reagents. A catalyst that condenses amino acids could have an important impact by reducing the significant waste generated during peptide synthesis. We describe the rational design of a biomimetic catalyst that can efficiently couple amino acids featuring standard protecting groups. The catalyst design combines lessons learned from enzymes, peptide biosynthesis, and organocatalysts. Under optimized conditions, 5 mol % catalyst efficiently couples Fmoc amino acids without notable racemization. Importantly, we demonstrate that the catalyst is functional for the synthesis of oligopeptides on solid phase. This result is significant because it illustrates the potential of the catalyst to function on a substrate with a multitude of amide bonds, which may be expected to inhibit a hydrogen-bonding catalyst.

Original languageEnglish (US)
Pages (from-to)15977-15985
Number of pages9
JournalJournal of the American Chemical Society
Volume141
Issue number40
DOIs
StatePublished - Oct 9 2019

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Amides
Peptides
Catalysts
Amino Acids
Peptide Biosynthesis
Amino acids
Oligopeptides
Biomimetics
Hydrogen Bonding
Polymers
Biosynthesis
Coupling agents
Drug products
Enzymes
Pharmaceutical Preparations
Hydrogen bonds
Availability
Proteins
Substrates

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Rational Design of an Organocatalyst for Peptide Bond Formation. / Handoko; Satishkumar, Sakilam; Panigrahi, Nihar R.; Arora, Paramjit S.

In: Journal of the American Chemical Society, Vol. 141, No. 40, 09.10.2019, p. 15977-15985.

Research output: Contribution to journalArticle

Handoko ; Satishkumar, Sakilam ; Panigrahi, Nihar R. ; Arora, Paramjit S. / Rational Design of an Organocatalyst for Peptide Bond Formation. In: Journal of the American Chemical Society. 2019 ; Vol. 141, No. 40. pp. 15977-15985.
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