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Racemic and Quasi-Racemic X-ray Structures of Cyclic Disulfide-Rich Peptide Drug Scaffolds
- Source :
- Angewandte Chemie International Edition. 53:11236-11241
- Publication Year :
- 2014
- Publisher :
- Wiley, 2014.
-
Abstract
- Cyclic disulfide-rich peptides have exceptional stability and are promising frameworks for drug design. We were interested in obtaining X-ray structures of these peptides to assist in drug design applications, but disulfide-rich peptides can be notoriously difficult to crystallize. To overcome this limitation, we chemically synthesized the L- and D-forms of three prototypic cyclic disulfide-rich peptides: SFTI-1 (14-mer with one disulfide bond), cVc1.1 (22-mer with two disulfide bonds), and kB1 (29-mer with three disulfide bonds) for racemic crystallization studies. Facile crystal formation occurred from a racemic mixture of each peptide, giving structures solved at resolutions from 1.25 Å to 1.9 Å. Additionally, we obtained the quasi-racemic structures of two mutants of kB1, [G6A]kB1, and [V25A]kB1, which were solved at a resolution of 1.25 Å and 2.3 Å, respectively. The racemic crystallography approach appears to have broad utility in the structural biology of cyclic peptides.
- Subjects :
- Models, Molecular
chemistry.chemical_classification
Racemic crystallography
Stereochemistry
Molecular Sequence Data
Stereoisomerism
Peptide
General Medicine
General Chemistry
Crystallography, X-Ray
Native chemical ligation
Peptides, Cyclic
Catalysis
Cyclic peptide
Structural biology
chemistry
Plant protein
Drug Design
Racemic mixture
Amino Acid Sequence
Disulfides
Crystallization
Subjects
Details
- ISSN :
- 14337851
- Volume :
- 53
- Database :
- OpenAIRE
- Journal :
- Angewandte Chemie International Edition
- Accession number :
- edsair.doi.dedup.....0924b161ce206423ee70487f35e7dbe7