{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/70289"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/70289","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"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","abstract":"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.","abstract_html":"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.","abstract_has_math":false,"creators":["Boulanger, William Allen"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2014,"date_issued":"2014-12-15T23:18:24Z","date_published":"2014-12-15T23:18:24Z","updated_at":"2026-07-22T22:26:02Z","subjects":["Chemistry, Organic"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["(UMI)AAI8511582"],"render_values":[{"text":"(UMI)AAI8511582","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2142/70289","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Boulanger, William Allen"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2014-12-15T23:18:24Z","10000-01-01","1985"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Chemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Chemistry, Organic"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/70289","(UMI)AAI8511582"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["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.","By removing the methylene of the benzyl pyrone to give 3-phenyl-6-chloro-2-pyranone, no irreversible inhibition was observed, though the compound proved to be a remarkably good competitive inhibitor (K(,i) = 0.27 uM). Computer models suggest that it may be a substrate sterically unable to ring-open. In contrast, 4-phenyl-6-chloro-2-pyranone is a very rapid inactivator of chymotrypsin, but the also rapid reactivation suggests that it mimics ethyl cinnamate and simply acylates serine.","6-Chloropyrones are faster inactivators than 6-bromopyrones; 6-proteopyrones bind more poorly than the 6-halopyrones, are not substrates, and do not inactivate chymotrypsin, indicating the need for ring-activation if this system is to be used as the basis of suicide inhibitors. Electron withdrawing, non-leaving groups such as 5- or 6-trifluoromethyl do not activate the pyrone in lieu of halogen.","Two kinds of 5-halomethyl-2-pyranones were surveyed as possible suicide inhibitors for chymotrypsin; 5-chloromethyl-2-pyranones and 5-trifluoromethyl-2-pyranones. Neither type proved to be a substrate, though the 5-chloromethyl pyrones inactivated chymotrypsin with great efficiency (1.38 to 2.0 equivalents), apparently by an affinity-labelling mechanism.","Made available in DSpace on 2014-12-15T23:18:24Z (GMT). No. of bitstreams: 1 8511582.pdf: 5472943 bytes, checksum: d2678c09489e964c2b2f218f1c66caa4 (MD5) Previous issue date: 1985","Embargo set by: Seth Robbins for item 70455 Lift date: Forever Reason: Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","U of I Only","181 p.","Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1985."]},{"key":"dc:title","label":"Title","values":["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"]}]}],"canonical_facts":{"dc:creator":["Boulanger, William Allen"],"dc:date":["2014-12-15T23:18:24Z","10000-01-01","1985"],"dc:description":["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.","By removing the methylene of the benzyl pyrone to give 3-phenyl-6-chloro-2-pyranone, no irreversible inhibition was observed, though the compound proved to be a remarkably good competitive inhibitor (K(,i) = 0.27 uM). Computer models suggest that it may be a substrate sterically unable to ring-open. In contrast, 4-phenyl-6-chloro-2-pyranone is a very rapid inactivator of chymotrypsin, but the also rapid reactivation suggests that it mimics ethyl cinnamate and simply acylates serine.","6-Chloropyrones are faster inactivators than 6-bromopyrones; 6-proteopyrones bind more poorly than the 6-halopyrones, are not substrates, and do not inactivate chymotrypsin, indicating the need for ring-activation if this system is to be used as the basis of suicide inhibitors. Electron withdrawing, non-leaving groups such as 5- or 6-trifluoromethyl do not activate the pyrone in lieu of halogen.","Two kinds of 5-halomethyl-2-pyranones were surveyed as possible suicide inhibitors for chymotrypsin; 5-chloromethyl-2-pyranones and 5-trifluoromethyl-2-pyranones. Neither type proved to be a substrate, though the 5-chloromethyl pyrones inactivated chymotrypsin with great efficiency (1.38 to 2.0 equivalents), apparently by an affinity-labelling mechanism.","Made available in DSpace on 2014-12-15T23:18:24Z (GMT). No. of bitstreams: 1 8511582.pdf: 5472943 bytes, checksum: d2678c09489e964c2b2f218f1c66caa4 (MD5) Previous issue date: 1985","Embargo set by: Seth Robbins for item 70455 Lift date: Forever Reason: Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","U of I Only","181 p.","Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1985."],"dc:identifier":["http://hdl.handle.net/2142/70289","(UMI)AAI8511582"],"dc:subject":["Chemistry, Organic"],"dc:title":["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"],"dc:type":["text"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:26:02Z"}