Modulation of calcium oxalate crystallization by linear aspartic acid-rich peptides.
Calcium oxalate monohydrate (COM) kidney stone formation is prevented in most humans by urinary crystallization inhibitors. Urinary osteopontin (OPN) is a prototype of the aspartic acid-rich proteins (AARP) that modulate biomineralization. Synthetic poly(aspartic acids) that resemble functional domains of AARPs provide surrogate molecules for exploring the role of AARPs in biomineralization. Effects of linear aspartic acid-rich peptides on COM growth kinetics and morphology were evaluated by the combination of constant composition (CC) analysis and atomic force microscopy (AFM). A spacer amino acid (either glycine or serine) was incorporated during synthesis after each group of 3 aspartic acids (DDD) in the 27-mer peptide sequences. Kinetic CC studies revealed that the DDD peptide with serine spacers (DDDS) was more than 30 times more effective in inhibiting COM crystal growth than the DDD peptide with glycine spacers (DDDG). AFM revealed changes in morphology on (010) and (-101) COM faces that were generally similar to those previously described for OPN and citrate, respectively. At comparable peptide levels, the effects of step pinning and reduced growth rate caused by DDDS were remarkably greater. In CC nucleation studies, DDDS caused a greater prolongation of induction periods than DDDG. Thus, nucleation studies link changes in interfacial energy caused by peptide adsorption to COM to the CC growth and AFM results. These studies indicate that, in addition to the number of acidic residues, the contributions of other amino acids to the conformation of DDD peptides are also important determinants of the inhibition of COM nucleation and growth.
Wang
Lijun
L
Department of Chemistry, Natural Sciences Complex, State University of New York at Buffalo, Buffalo, New York 14260, USA.
Qiu
S Roger
SR
Zachowicz
William
W
Guan
Xiangying
X
Deyoreo
James J
JJ
Nancollas
George H
GH
Hoyer
John R
JR
D000595:Amino Acid Sequence; D001224:Aspartic Acid / Q000737:chemistry*; D002129:Calcium Oxalate / Q000737:chemistry*; D003460:Crystallization; D018625:Microscopy, Atomic Force; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*
D010455:Peptides; D002129:Calcium Oxalate; D001224:Aspartic Acid