Crystal Growth Inhibitors for the Prevention of L-Cystine Kidney Stones Through Molecular Design

Department of Chemistry and the Molecular Design Institute, New York University (NYU), 100 Washington Square East, New York, NY 10003-6688, USA.
Science (Impact Factor: 33.61). 10/2010; 330(6002):337-41. DOI: 10.1126/science.1191968
Source: PubMed


Crystallization of L-cystine is a critical step in the pathogenesis of cystine kidney stones. Treatments for this disease are somewhat effective but often lead to adverse side effects. Real-time in situ atomic force microscopy (AFM) reveals that L-cystine dimethylester (L-CDME) and L-cystine methylester (L-CME) dramatically reduce the growth velocity of the six symmetry-equivalent {100} steps because of specific binding at the crystal surface, which frustrates the attachment of L-cystine molecules. L-CDME and L-CME produce l-cystine crystals with different habits that reveal distinct binding modes at the crystal surfaces. The AFM observations are mirrored by reduced crystal yield and crystal size in the presence of L-CDME and L-CME, collectively suggesting a new pathway to the prevention of L-cystine stones by rational design of crystal growth inhibitors.

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    • "Hexagonal crystals contain helices spanning six molecules of L-cystine that interact with each other with strong NH 3 + … -O(C=O) hydrogen and S…S disulfide bonds (Oughton and Harrison 1959;Rimer et al. 2010). Other molecules facilitating the initial interaction between molecules of L-cystine may have a prominent role in promoting nucleation. "
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