L-胱氨酸二酰胺作为胱氨酸尿症中L-胱氨酸结晶抑制剂
l-Cystine Diamides as l-Cystine Crystallization Inhibitors for Cystinuria.
作者信息
Hu Longqin, Yang Yanhui, Aloysius Herve, Albanyan Haifa, Yang Min, Liang Jian-Jie, Yu Anthony, Shtukenberg Alexander, Poloni Laura N, Kholodovych Vladyslav, Tischfield Jay A, Goldfarb David S, Ward Michael D, Sahota Amrik
机构信息
Department of Medicinal Chemistry, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey , 160 Frelinghuysen Road, Piscataway, New Jersey 08854, United States.
Department of Genetics, Rutgers, The State University of New Jersey , Piscataway, New Jersey 08854, United States.
出版信息
J Med Chem. 2016 Aug 11;59(15):7293-8. doi: 10.1021/acs.jmedchem.6b00647. Epub 2016 Jul 26.
Abstract
l-Cystine bismorpholide (1a) and l-cystine bis(N'-methylpiperazide) (1b) were seven and twenty-four times more effective than l-cystine dimethyl ester (CDME) in increasing the metastable supersaturation range of l-cystine, respectively, effectively inhibiting l-cystine crystallization. This behavior can be attributed to inhibition of crystal growth at microscopic length scale, as revealed by atomic force microscopy. Both 1a and 1b are more stable than CDME, and 1b was effective in vivo in a knockout mouse model of cystinuria.
摘要
L-胱氨酸双吗啉代酯（1a）和L-胱氨酸双（N'-甲基哌嗪）（1b）在增加L-胱氨酸的亚稳过饱和范围方面分别比L-胱氨酸二甲酯（CDME）有效7倍和24倍，能有效抑制L-胱氨酸结晶。如原子力显微镜所示，这种行为可归因于在微观长度尺度上对晶体生长的抑制。1a和1b都比CDME更稳定，并且1b在胱氨酸尿症基因敲除小鼠模型中在体内有效。
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