Zinc-Binding Groups Modulate Selective Inhibition of MMPs
نویسندگان
چکیده
منابع مشابه
Computational exploration of zinc binding groups for HDAC inhibition.
Histone deacetylases (HDACs) have emerged as important drug targets in epigenetics. The most common HDAC inhibitors use hydroxamic acids as zinc binding groups despite unfavorable pharmacokinetic properties. A two-stage protocol of M05-2X calculations of a library of 48 fragments in a small model active site, followed by QM/MM hybrid calculations of the full enzyme with selected binders, is use...
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2-Azetidinones, commonly known as beta-lactams, are well-known heterocyclic compounds. Herein we described the synthesis and biological evaluation of a series of novel beta-lactams. In vitro inhibition assays against HDAC isoforms showed an interesting isoform-selectivity of these compounds towards HDAC6 and HDAC8. The isoform selectivity changed in response to modification of the azetidinone-r...
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The relative binding affinity of Zn2+ to several glycosaminoglycans was determined by gel-filtration chromatography. Binding was observed only between Zn2+ and heparin. No binding was observed between Zn2+ and chondroitin 4-sulphate, chondroitin 6-sulphate, dermatan sulphate or hyaluronic acid. All of the glycosaminoglycans contained carboxy groups, but only heparin bound Zn2+. This observation...
متن کاملAmino Acid Derivatives as New Zinc Binding Groups for the Design of Selective Matrix Metalloproteinase Inhibitors
A number of matrix metalloproteinases (MMPs) are important medicinal targets for conditions ranging from rheumatoid arthritis to cardiomyopathy, periodontal disease, liver cirrhosis, multiple sclerosis, and cancer invasion and metastasis, where they showed to have a dual role, inhibiting or promoting important processes involved in the pathology. MMPs contain a zinc (II) ion in the protein acti...
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The prognostic value of matrix metalloproteinases has been evaluated since many years for its role in tissue remodeling events. The need for selective inhibition of the matrix metalloproteinases is to be of great interest due to the various side effects caused by MMP isoforms. The search for high affinity zinc binding groups that effectively inhibit MMP catalytic site is believed to serve as a ...
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ژورنال
عنوان ژورنال: ChemMedChem
سال: 2008
ISSN: 1860-7179,1860-7187
DOI: 10.1002/cmdc.200700290