Crystal growth inhibitors for the prevention of L-cystine kidney stones through molecular design.
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.
Rimer
Jeffrey D
JD
Department of Chemistry and the Molecular Design Institute, New York University, 100 Washington Square East, New York, NY 10003-6688, USA.
An
Zhihua
Z
Department of Chemistry and the Molecular Design Institute, New York University, 100 Washington Square East, New York, NY 10003-6688, USA.
Zhu
Zina
Z
Department of Chemistry and the Molecular Design Institute, New York University, 100 Washington Square East, New York, NY 10003-6688, USA.
Lee
Michael H
MH
Department of Chemistry and the Molecular Design Institute, New York University, 100 Washington Square East, New York, NY 10003-6688, USA.
Goldfarb
David S
DS
Nephrology Section, New York Harbor VAMC, Department of Urology, St. Vincent's Hospital and NYU School of Medicine, New York, NY.
Wesson
Jeffrey A
JA
Nephrology Division, Department of Veterans Affairs Medical Center and the Medical College of Wisconsin, 5000 West National Avenue, Milwaukee, WI 53295.
Ward
Michael D
MD
Department of Chemistry and the Molecular Design Institute, New York University, 100 Washington Square East, New York, NY 10003-6688, USA.
D001665:Binding Sites; D055598:Chemical Phenomena; D003460:Crystallization; D003553:Cystine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D003555:Cystinuria / Q000150:complications / Q000188:drug therapy*; D015195:Drug Design; D006801:Humans; D006860:Hydrogen Bonding; D007669:Kidney Calculi / Q000737:chemistry / Q000209:etiology / Q000517:prevention & control*; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D018716:Molecular Mimicry; D015394:Molecular Structure; D012995:Solubility
C553309:L-cystine dimethylester; C553308:L-cystine methylester; D003553:Cystine