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Abstract Thioamides, single atom oxygen‐to‐sulfur substitutions of canonical amide bonds, can be valuable probes for protein folding and protease studies. Here, we investigate the fluorescence quenching properties of thioamides incorporated into the side‐chains of amino acids. We synthesize and incorporate Fmoc‐protected, solid‐phase peptide synthesis building blocks for introducingNε‐thioacetyl‐lysine andγ‐thioasparagine. Using rigid model peptides, we demonstrate the distance‐dependent fluorescence quenching of these thioamides. Furthermore, we describe attempts to incorporate ofNε‐thioacetyl‐lysine into proteins expressed inEscherichia coliusing amber codon suppression.
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Rational Design of an Organocatalyst for Peptide Bond Formation
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.
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- Award ID(s):
- 1807670
- PAR ID:
- 10180597
- Date Published:
- Journal Name:
- Journal of the American Chemical Society
- Volume:
- 141
- Issue:
- 40
- ISSN:
- 0002-7863
- Page Range / eLocation ID:
- 15977–15985
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1021/jacs.9b07742
