+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Identification of novel polyphenol oxidase inhibitors by enzymatic one-pot synthesis and deconvolution of combinatorial libraries



Identification of novel polyphenol oxidase inhibitors by enzymatic one-pot synthesis and deconvolution of combinatorial libraries



Biotechnology & Bioengineering 75(1): 93-99



The feasibility of enzymatic synthesis of combinatorial libraries using multifunctional starting materials (i.e., 2,4-dihydroxy-N-(2-hydroxyethyl)benzamide, 1; 4-hydroxyphenethyl alcohol, 2; 3,5-dihydroxybenzyl alcohol, 3; and 4-hydroxybenzyl alcohol, 4) with six vinyl esters, in a one-pot reaction, was investigated. Candida antarctica lipase was employed as a biocatalyst. The resulting 24-compound library contained all the expected species with no significant bias toward particular combinations of substrates. As expected, the library contained a substance(s) that showed significant inhibition of polyphenol oxidase, which was used as a model target. The deconvolution was accomplished via resynthesis of ten partial libraries, which were prepared with either an equimolar mixture of the four alcohols and a single vinyl ester, or a single alcohol and equimolar mixture of the activated esters. Analysis of the inhibition pattern observed with these partial libraries suggested that 4-hydroxybenzyl benzoate (4e) should be the most potent inhibitor. This conclusion was confirmed by the preparation and comparison of all 24 components of the initial library. Finally, it was shown that 4e was a competitive inhibitor of polyphenol oxidase, with a Ki of 40 muM. This value compared favorably with a Ki of 400 muM, which was determined for parent phenol 4.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 010787276

Download citation: RISBibTeXText

PMID: 11536131

DOI: 10.1002/bit.1168


Related references

Cyclic peptide template combinatorial libraries: synthesis and identification of chymotrypsin inhibitors. Peptide Research 7(6): 300-307, 1994

Use of parallel-synthesis combinatorial libraries for rapid identification of potent FKBP12 inhibitors. Bioorganic & Medicinal Chemistry Letters 12(10): 1421-1428, 2002

Synthesis of new self-encoded beads for the dual recursive deconvolution of resin-supported combinatorial libraries. Abstracts of Papers American Chemical Society 222(1-2): ORGN506, 2001

Research on enzymatic nature of polyphenol oxidase from Trametes trogii and the enzymatic synthesis of theaflavins. Journal Of Tea Science: 5, 326-330, 2008

Synthesis, folding and deconvolution of combinatorial peptide libraries based on alpha-conotoxins Generation of a novel ligand for alpha7 nicotinic acetylcholine receptor. Biopolymers 71(3): 356, 2003

Synthesis and deconvolution of the first combinatorial library of glycosidase inhibitors. Bioorganic and Medicinal Chemistry 7(9): 1965-1971, 1999

Identification of enzyme inhibitors using combinatorial libraries. Current Medicinal Chemistry 9(3): 307-319, 2002

Identification of Enzyme Inhibitors Using Combinatorial Libraries. Current Medicinal Chemistry 9(3): 307-319, 2002

The identification of cyclooxygenase-1 inhibitors from 4-thiazolidinone combinatorial libraries. Bioorganic & Medicinal Chemistry Letters 6(6): 707-712, 1996

Identification of inhibitors of melittin using nonsupport-bound combinatorial libraries. Journal of Biological Chemistry 271(8): 4093-4099, 1996

Identification of broad-based HIV-1 protease inhibitors from combinatorial libraries. Biochemical Journal 429(3): 527-532, 2010

Identification of inhibitors of beta-amyloid neurotoxicity from synthetic combinatorial libraries. FASEB Journal 14(4): A635, 2000

Identification of highly selective inhibitors of collagenase-1 from combinatorial libraries of diketopiperazines. Journal of Medicinal Chemistry 42(8): 1348-1357, 1999

Identification of enzyme inhibitors from phage-displayed combinatorial peptide libraries. Combinatorial Chemistry & High Throughput Screening 4(7): 535-543, 2001

Combinatorial libraries from scaffolds Synthesis of orthogonal protected scaffolds and their use in solid phase synthesis of peptidomimetic combinatorial libraries. Abstracts Of Papers American Chemical Society. 216(1-3): Medi 159, 1998