کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5508951 | 1538393 | 2017 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Addition of thiols to the double bond of dipeptide C-terminal dehydroalanine as a source of new inhibitors of cathepsin C
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Addition of thiols to the double bond of dipeptide C-terminal dehydroalanine as a source of new inhibitors of cathepsin C Addition of thiols to the double bond of dipeptide C-terminal dehydroalanine as a source of new inhibitors of cathepsin C](/preview/png/5508951.png)
چکیده انگلیسی
Addition of thiols to double bond of glycyl-dehydroalanine and phenyl-dehydroalanine esters provided micromolar inhibitors of cathepsin C. The structure-activity studies indicated that dipeptides containing N-terminal phenylalanine exhibit higher affinity towards the enzyme. A series of C-terminal S-substituted cysteines are responsible for varying interaction with S1 binding pocket of cathepsin C. Depending on diastereomer these compounds most likely act as slowly reacting substrates or competitive inhibitors. This was proved by TLC analysis of the medium in which interaction of methyl (S)-phenylalanyl-(R,S)-(S-adamantyl)cysteinate (7i) with the enzyme was studied. Molecular modeling enabled to establish their mode of binding showed that S2 pocket is long and narrow and accommodates phenyl group of phenylalanine while significantly spacious sites located at the surface of the enzyme (one of them being S1 pocket) bind the adamantyl moiety oriented in different direction for each stereoisomer. Finally replacement of carboxymethyl moiety of methyl (S)-phenylalanyl-(R,S)-(S-phenyl)cysteinate (7c) with nitrile group provided about 650-times more potent inhibitor of cathepsin C indicating that the studied C-terminal S-substituted cysteines are good activity probes for S1 binding pocket of this enzyme.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimie - Volume 139, August 2017, Pages 46-55
Journal: Biochimie - Volume 139, August 2017, Pages 46-55
نویسندگان
PaweÅ Lenartowicz, Maciej Makowski, Bartosz Oszywa, Kinga Haremza, RafaÅ Latajka, MaÅgorzata PaweÅczak, PaweÅ Kafarski,