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Publication Abstract from PubMed

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 A to 1.9 A. 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 A and 2.3 A, respectively. The racemic crystallography approach appears to have broad utility in the structural biology of cyclic peptides.

Racemic and Quasi-Racemic X-ray Structures of Cyclic Disulfide-Rich Peptide Drug Scaffolds.,Wang CK, King GJ, Northfield SE, Ojeda PG, Craik DJ Angew Chem Int Ed Engl. 2014 Aug 28. doi: 10.1002/anie.201406563. PMID:25168664^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.