Department of Chemistry and the Molecular Design Institute, New York University, 100 Washington Square East, New York, NY 10003-6688, USA.
Nephrology Section, New York Harbor VAMC, Department of Urology, St. Vincent's Hospital and NYU School of Medicine, New York, NY.
Science. 2010 Oct 15;330(6002):337-341. doi: 10.1126/science.1191968.
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.
L-胱氨酸的结晶是胱氨酸肾结石发病机制中的关键步骤。该疾病的治疗方法有些有效,但往往会导致不良反应。实时原位原子力显微镜 (AFM) 揭示,L-胱氨酸二甲酯 (L-CDME) 和 L-胱氨酸甲酯 (L-CME) 通过在晶体表面的特异性结合,显著降低了六个对称等效 {100} 台阶的生长速度,因为这会阻碍 L-胱氨酸分子的附着。L-CDME 和 L-CME 生成具有不同习性的 l-胱氨酸晶体,在晶体表面呈现出不同的结合模式。AFM 观察结果反映在 L-CDME 和 L-CME 存在时晶体产率和晶体尺寸降低,这共同表明通过合理设计晶体生长抑制剂来预防 L-胱氨酸结石的新途径。