𝔖 Bobbio Scriptorium
✦   LIBER   ✦

New Potent Sialyltransferase Inhibitors—Synthesis of Donor and of Transition-State Analogues of Sialyl Donor CMP-Neu5Ac

✍ Scribed by Franz Amann; Christoph Schaub; Bernd Müller; Richard R. Schmidt

Publisher
John Wiley and Sons
Year
1998
Tongue
English
Weight
286 KB
Volume
4
Category
Article
ISSN
0947-6539

No coin nor oath required. For personal study only.

✦ Synopsis

Enzymatic sialyl transfer with CMP-Neu5Ac as donor can be inhibited by CDP. Therefore phosphonates 1 a,b, 2 and 3 were synthesized as substrate analogues. With a(2 ± 6)-sialyltransferase from rat liver (EC 2.4.99.1) only moderate inhibition was found for these compounds. In order to obtain transition-state analogues of CMP-Neu5Ac different linkages between 2,3-dehydro-N-acetylneuraminol and CMP were generated, yielding 4, (R)-5 and (R)-6. Compound (R)-6, in which the CMP residue is attached to C-1 of 2,3-dehydro-N-acetylneuramin-1-yl phosphonate, exhibited excellent a(2 ± 6)-sialyltransferase inhibition in the nanomolar range (K i 350 nm), resulting in a 130-fold higher affinity for the enzyme than CMP-Neu5Ac (K M 46 mm).

📜 SIMILAR VOLUMES

Efficient Sialyltransferase Inhibitors B
Efficient Sialyltransferase Inhibitors Based on Transition-State Analogues of the Sialyl Donor
✍ Bernd Müller; Christoph Schaub; Richard R. Schmidt 📂 Article 📅 1998 🏛 John Wiley and Sons 🌐 English ⚖ 161 KB 👁 1 views

A 200- to 1000-fold higher affinity for sialyltransferase is shown by compounds 1 and 2 relative to the natural substrate. These inhibitors, which are derived from the transition state of S 1-type sialyltransfer, contain a flat ring that is attached through a carbon atom with a phosphonate and a cyt

ChemInform Abstract: Synthesis of a New
ChemInform Abstract: Synthesis of a New Transition-State Analogue of the Sialyl Donor. Inhibition of Sialyltransferases.
✍ Hongbin Sun; Jingsong Yang; Katie E. Amaral; Benjamin A. Horenstein 📂 Article 📅 2010 🏛 John Wiley and Sons ⚖ 32 KB 👁 1 views

## Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable v

ChemInform Abstract: Synthesis of a New
ChemInform Abstract: Synthesis of a New Class of N-Linked Lewis and LacNAc Analogues as Potential Inhibitors of Human Fucosyltransferases: A General Method for the Incorporation of an Iminocyclitol as a Transition-State Mimetic of the Donor Sugar to the Acceptor.
✍ Ralf Wischnat; Richard Martin; Chi-Huey Wong 📂 Article 📅 2010 🏛 John Wiley and Sons ⚖ 35 KB 👁 2 views

Synthesis of a New Class of N-Linked Lewis and LacNAc Analogues as Potential Inhibitors of Human Fucosyltransferases: A General Method for the Incorporation of an Iminocyclitol as a Transition-State Mimetic of the Donor Sugar to the Acceptor. -The synthesis of the title N-linked di-and trisaccharid