2-Pyranones as Suicide Inhibitors for Alpha-Chymotrypsin: I. A Structure-Activity Study of the 6-Halo-2-Pyranones. Ii. 5-Halomethyl-2-Pyranones as Inhibitors of Chymotrypsin

A structure-activity study was done on a series of 6-halo-2-pyranones as suicide inhibitors of chymotrypsin. In the 6-chloro-2-pyranone series, substitution in the 3- position of the pyrone by either ethyl or n-butyl produced poor binding relative to 3-benzyl-6-chloro-2-pyranone, and no inactivation. Increasing the aromatic area of the binding group by replacing the benzyl group with a naphthylmethyl had a dramatically different effect, depending upon the naphthyl substitution; 3-(2-naphthyl)methyl-6-chloro-2-pyranone inhibited chymotrypsin 33-fold faster than the benzyl pyrone and 100-fold faster than the 1-naphthyl isomer. Models suggest that this great difference is a consequence of binding, not steric inhibition.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2014

Author dc:creator

• Boulanger, William Allen

• Chemistry, Organic

Identifier

(UMI)AAI8511582

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/70289