Role of Molecular Recognition in l -Cystine Crystal Growth Inhibition

Laura N. Poloni, Zina Zhu, Nelson Garcia-Vázquez, Anthony C. Yu, David M. Connors, Longqin Hu, Amrik Sahota, Michael D. Ward, Alexander G. Shtukenberg

Research output: Contribution to journalArticlepeer-review


l-Cystine kidney stones - aggregates of single crystals of the hexagonal form of l-cystine - afflict more than 20 000 individuals in the United States alone. Current therapies are often ineffective and produce adverse side effects. Recognizing that the growth of l-cystine crystals is a critical step in stone pathogenesis, real-time in situ atomic force microscopy of growth on the (0001) face of l-cystine crystals and measurements of crystal growth anisotropy were performed in the presence of prospective inhibitors drawn from a 31-member library. The most effective molecular imposters for crystal growth inhibition were l-cystine mimics (aka molecular imposters), particularly l-cystine diesters and diamides, for which a kinetic analysis revealed a common inhibition mechanism consistent with Cabrera-Vermilyea step pinning. The amount of inhibitor incorporated by l-cystine crystals, estimated from kinetic data, suggests that imposter binding to the {0001} face is less probable than binding of l-cystine solute molecules, whereas imposter binding to {1010} faces is comparable to that of l-cystine molecules. These estimates were corroborated by computational binding energies. Collectively, these findings identify the key structural factors responsible for molecular recognition between molecular imposters and l-cystine crystal kink sites, and the inhibition of crystal growth. The observations are consistent with the reduction of l-cystine stone burden in mouse models by the more effective inhibitors, thereby articulating a strategy for stone prevention based on molecular design.

Original languageEnglish (US)
Pages (from-to)2767-2781
Number of pages15
JournalCrystal Growth and Design
Issue number5
StatePublished - May 3 2017

ASJC Scopus subject areas

  • General Chemistry
  • General Materials Science
  • Condensed Matter Physics


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