AI Article Synopsis
- Researchers developed and tested various l-cystine diamides to enhance the stability of l-cystine dimethyl ester (CDME) and l-cystine methyl ester (CME) while inhibiting l-cystine crystallization.
- They discovered that l-cystine diamides without N-methylation effectively prevented l-cystine crystallization, whereas those with N-methylation lost this ability.
- Computational studies revealed that N-methylation reduces the binding affinity of these diamides to the l-cystine crystal surface, with l-cystine bismorpholide and l-cystine bis(N'-methylpiperazide) identified as the most potent inhibitors.
Article Abstract
To overcome the chemical and metabolic stability issues of l-cystine dimethyl ester (CDME) and l-cystine methyl ester (CME), a series of l-cystine diamides with or without N-methylation was designed, synthesized, and evaluated for their inhibitory activity of l-cystine crystallization. l-Cystine diamides 2a-i without N-methylation were found to be potent inhibitors of l-cystine crystallization while N-methylation of l-cystine diamides resulted in derivatives 3b-i devoid of any inhibitory activity of l-cystine crystallization. Computational modeling indicates that N-methylation leads to significant decrease in binding of the l-cystine diamides to l-cystine crystal surface. Among the l-cystine diamides 2a-i, l-cystine bismorpholide (CDMOR, LH707, 2g) and l-cystine bis(N'-methylpiperazide) (CDNMP, LH708, 2h) are the most potent inhibitors of l-cystine crystallization.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5893393 | PMC |
| http://dx.doi.org/10.1016/j.bmcl.2018.03.024 | DOI Listing |
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