ProHealth health Vitamin and Natural Supplement Store and Health
Log In  |  My Account  |  View Cart  View Your ProHealth Vitamin and Supplement Shopping Cart
800-366-6056  |  Contact Us  |  Help

|
|
|
|

Trending News

Missing protein explains link between obesity, diabetes

Fish oil use associated with brain volume preservation

The Brain Boosting and Fatigue Fighting B-12

Genetic basis for distinct type of autism uncovered

Unsuspected aspect of immune regulation revealed: Role of B cells

IBS, Crohn’s Disease, Colitis, and Other Digestive Disorders

Explaining 'Healthy' Obesity

Sinus Congestion and Sinusitis, Healing Naturally

In the gut, immunity is a two-way street

Omega 3 Fatty Acids Lessen Severity of Osteoarthritis in Mice

 
Print Page
Email Article

Abstract: Probing the activation site of ribonuclease L with new N(6)-substituted 2',5'-adenylate trimers

  [ 7 votes ]   [ Discuss This Article ]
www.ProHealth.com • April 9, 2003


Bioorg Med Chem 2003 May;11(9):2041-9

Munch U, Chen L, Bayly SF, Torrence PF.

Section on Biomedical Chemistry, Laboratory of Medicinal Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, MD 20892-0805, Bethesda, USA

2-5A trimer [5'-monophosphoryladenylyl(2'-5')adenylyl(2'-5')adenosine] activates RNase L. While the 5'-terminal and 2'-terminal adenosine N(6)-amino groups play a key role in binding to and activation of RNase L, the exocyclic amino function of the second adenylate (from the 5'-terminus) plays a relatively minor role in 2-5A's biological activity.

To probe the available space proximal to the amino function of the central adenylate of 2-5A trimer during binding to RNase L, a variety of substituents were placed at that position. To accomplish this, the convertible building block 5'-O-dimethoxytrityl-3'-O-(tert-butyldimethylsilyl)-6-(2,4-dinitrophenyl)thioinosine 2'-(2-cyanoethylN,N-diisopropylphosphoramidite) was prepared as a synthon to introduce 6-(2,4-dinitrophenyl)thioinosine into the middle position of the 2-5A trimer during automated synthesis. Post-synthetic treatment with aqueous amines transformed the (2,4-dinitrophenyl)thioinosine into N(6)-substituted adenosines.

Assays of these modified trimers for their ability to bind and activate RNase L showed that activation activity could be retained, albeit with some sacrifice compared to unmodified p5'A2'p5'A2'p5'A.

Thus, the spatial domain about thisN(6)-amino function could be available for modifications to enhance the biological potency of 2-5A analogues and to ligate 2-5A to targeting vehicles such as antisense molecules.

PMID: 12670655 [PubMed - in process]




Discuss This Article Post a Comment 




[ Be the first to comment on this article ]




 
Free Chronic Fatigue Syndrome and Fibromyalgia Newsletters
Subscribe to
Our FREE
Newsletter
Subscribe Now!
Receive up-to-date ME/CFS & Fibromyalgia treatment and research news
 Privacy Guaranteed  |  View Archives

Featured Products

Ultra ATP+, Double Strength Ultra ATP+, Double Strength
Get energized with malic acid & magnesium
Vitamin D3 Extreme™ by ProHealth Vitamin D3 Extreme™ by ProHealth
50,000 IU Vitamin D3 - Prescription Strength
FibroSleep™ by ProHealth FibroSleep™ by ProHealth
The All-in-One Natural Sleep Aid
Optimized Curcumin Longvida® by ProHealth Optimized Curcumin Longvida® by ProHealth
Supports Cognition, Memory & Overall Health
Energy NADH™ 12.5mg Energy NADH™ 12.5mg
Improve Energy & Cognitive Function

Natural Remedies

Sweet Tips for Fibromyalgia Success
Reversing Neurodegeneration with a New Magnesium Compound Reversing Neurodegeneration with a New Magnesium Compound
More Weight Loss than Any Other Discovery in Supplement History More Weight Loss than Any Other Discovery in Supplement History
The Revolutionary 'Good Fat' That Promotes Heart, Brain, Bone and Joint Health The Revolutionary 'Good Fat' That Promotes Heart, Brain, Bone and Joint Health
Natural Support for Mood, Sleep and Mental Focus? L-theanine Natural Support for Mood, Sleep and Mental Focus? L-theanine

FIBROMYALGIA RESOURCES
What is Fibromyalgia?
Fibromyalgia 101
Fibromyalgia Symptoms
Fibromyalgia Treatments
| CFS RESOURCES
What is CFS?
ME/CFS 101
ME/CFS Symptoms
ME/CFS Treatments
| FORUMS
Fibromyalgia
ME/CFS
ADVANCED MEDICAL LABS
WHOLESALE  |  AFFILIATES
GUARANTEE
CONTACT US
PRIVACY
RSS
SITE MAP
ProHealth on Facebook  ProHealth on Twitter  ProHealth on Pinterest  ProHealth on Google Plus
Credit Card Processing