Trimethyl lock: a trigger for molecular release in chemistry, biology, and pharmacology

The trimethyl lock is an o -hydroxydihydrocinnamic acid derivative in which unfavorable steric interactions between three pendant methyl groups encourage lactonization to form a hydrocoumarin. This reaction is extremely rapid, even when the electrophile is an amide and the leaving group is an amino...

Full description

Saved in:
Bibliographic Details
Published in:Chemical science (Cambridge) 2012-01, Vol.3 (8), p.2412-242
Main Authors: Levine, Michael N, Raines, Ronald T
Format: Article
Language:English
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c492t-c53c547b6f0c513fc474e566f4cbb595e1b7793ee4de178b9f2751d401d610f93
cites cdi_FETCH-LOGICAL-c492t-c53c547b6f0c513fc474e566f4cbb595e1b7793ee4de178b9f2751d401d610f93
container_end_page 242
container_issue 8
container_start_page 2412
container_title Chemical science (Cambridge)
container_volume 3
creator Levine, Michael N
Raines, Ronald T
description The trimethyl lock is an o -hydroxydihydrocinnamic acid derivative in which unfavorable steric interactions between three pendant methyl groups encourage lactonization to form a hydrocoumarin. This reaction is extremely rapid, even when the electrophile is an amide and the leaving group is an amino group of a small-molecule drug, fluorophore, peptide, or nucleic acid. O -Acylation of the phenolic hydroxyl group prevents reaction, providing a trigger for the reaction. Thus, the release of an amino group from an amide can be coupled to the hydrolysis of a designated ester (or to another chemical reaction that regenerates the hydroxyl group). Trimethyl lock conjugates are easy to synthesize, making the trimethyl lock a highly versatile module for chemical biology and related fields. The trimethyl lock provides unmatched attributes as a trigger for the release of small molecules by an enzymatic, chemical, or photolytic process.
doi_str_mv 10.1039/c2sc20536j
format article
fullrecord <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3501758</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>23181187</sourcerecordid><originalsourceid>FETCH-LOGICAL-c492t-c53c547b6f0c513fc474e566f4cbb595e1b7793ee4de178b9f2751d401d610f93</originalsourceid><addsrcrecordid>eNp9kE1Lw0AQhhdRbKm9eFfWqxjdz2ziQZDiFxS8VDwum81ukppky24q9N8braZ6cS4zzDzzDvMCcIzRJUY0vdIkaII4jZd7YEwQw1HMabo_1ASNwDSEJeqDUsyJOAQjQnGCcSLG4HXhq8Z05aaGtdNv11DBzldFYTy0zsPG1Uava-WhN7VRwcCqhbo0TRU6v7mAWeVqV_SFanO4KpVvlP7qHIEDq-pgpt95Al7u7xazx2j-_PA0u51HmqWkizSnmjORxRZpjqnVTDDD49gynWU85QZnQqTUGJYbLJIstURwnDOE8xgjm9IJuNnqrtZZY3Jt2s6rWq76r5TfSKcq-XfSVqUs3LukHGHBk17gfCugvQvBGzvsYiQ_HZY7h3v49Pe1Af3xswfOtoAPepjuBOQqtz1z8h9DPwArAY3V</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Trimethyl lock: a trigger for molecular release in chemistry, biology, and pharmacology</title><source>Royal Society of Chemistry</source><creator>Levine, Michael N ; Raines, Ronald T</creator><creatorcontrib>Levine, Michael N ; Raines, Ronald T</creatorcontrib><description>The trimethyl lock is an o -hydroxydihydrocinnamic acid derivative in which unfavorable steric interactions between three pendant methyl groups encourage lactonization to form a hydrocoumarin. This reaction is extremely rapid, even when the electrophile is an amide and the leaving group is an amino group of a small-molecule drug, fluorophore, peptide, or nucleic acid. O -Acylation of the phenolic hydroxyl group prevents reaction, providing a trigger for the reaction. Thus, the release of an amino group from an amide can be coupled to the hydrolysis of a designated ester (or to another chemical reaction that regenerates the hydroxyl group). Trimethyl lock conjugates are easy to synthesize, making the trimethyl lock a highly versatile module for chemical biology and related fields. The trimethyl lock provides unmatched attributes as a trigger for the release of small molecules by an enzymatic, chemical, or photolytic process.</description><identifier>ISSN: 2041-6520</identifier><identifier>EISSN: 2041-6539</identifier><identifier>DOI: 10.1039/c2sc20536j</identifier><identifier>PMID: 23181187</identifier><language>eng</language><publisher>England</publisher><ispartof>Chemical science (Cambridge), 2012-01, Vol.3 (8), p.2412-242</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c492t-c53c547b6f0c513fc474e566f4cbb595e1b7793ee4de178b9f2751d401d610f93</citedby><cites>FETCH-LOGICAL-c492t-c53c547b6f0c513fc474e566f4cbb595e1b7793ee4de178b9f2751d401d610f93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23181187$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Levine, Michael N</creatorcontrib><creatorcontrib>Raines, Ronald T</creatorcontrib><title>Trimethyl lock: a trigger for molecular release in chemistry, biology, and pharmacology</title><title>Chemical science (Cambridge)</title><addtitle>Chem Sci</addtitle><description>The trimethyl lock is an o -hydroxydihydrocinnamic acid derivative in which unfavorable steric interactions between three pendant methyl groups encourage lactonization to form a hydrocoumarin. This reaction is extremely rapid, even when the electrophile is an amide and the leaving group is an amino group of a small-molecule drug, fluorophore, peptide, or nucleic acid. O -Acylation of the phenolic hydroxyl group prevents reaction, providing a trigger for the reaction. Thus, the release of an amino group from an amide can be coupled to the hydrolysis of a designated ester (or to another chemical reaction that regenerates the hydroxyl group). Trimethyl lock conjugates are easy to synthesize, making the trimethyl lock a highly versatile module for chemical biology and related fields. The trimethyl lock provides unmatched attributes as a trigger for the release of small molecules by an enzymatic, chemical, or photolytic process.</description><issn>2041-6520</issn><issn>2041-6539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><recordid>eNp9kE1Lw0AQhhdRbKm9eFfWqxjdz2ziQZDiFxS8VDwum81ukppky24q9N8braZ6cS4zzDzzDvMCcIzRJUY0vdIkaII4jZd7YEwQw1HMabo_1ASNwDSEJeqDUsyJOAQjQnGCcSLG4HXhq8Z05aaGtdNv11DBzldFYTy0zsPG1Uava-WhN7VRwcCqhbo0TRU6v7mAWeVqV_SFanO4KpVvlP7qHIEDq-pgpt95Al7u7xazx2j-_PA0u51HmqWkizSnmjORxRZpjqnVTDDD49gynWU85QZnQqTUGJYbLJIstURwnDOE8xgjm9IJuNnqrtZZY3Jt2s6rWq76r5TfSKcq-XfSVqUs3LukHGHBk17gfCugvQvBGzvsYiQ_HZY7h3v49Pe1Af3xswfOtoAPepjuBOQqtz1z8h9DPwArAY3V</recordid><startdate>20120101</startdate><enddate>20120101</enddate><creator>Levine, Michael N</creator><creator>Raines, Ronald T</creator><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20120101</creationdate><title>Trimethyl lock: a trigger for molecular release in chemistry, biology, and pharmacology</title><author>Levine, Michael N ; Raines, Ronald T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c492t-c53c547b6f0c513fc474e566f4cbb595e1b7793ee4de178b9f2751d401d610f93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Levine, Michael N</creatorcontrib><creatorcontrib>Raines, Ronald T</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Chemical science (Cambridge)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Levine, Michael N</au><au>Raines, Ronald T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Trimethyl lock: a trigger for molecular release in chemistry, biology, and pharmacology</atitle><jtitle>Chemical science (Cambridge)</jtitle><addtitle>Chem Sci</addtitle><date>2012-01-01</date><risdate>2012</risdate><volume>3</volume><issue>8</issue><spage>2412</spage><epage>242</epage><pages>2412-242</pages><issn>2041-6520</issn><eissn>2041-6539</eissn><abstract>The trimethyl lock is an o -hydroxydihydrocinnamic acid derivative in which unfavorable steric interactions between three pendant methyl groups encourage lactonization to form a hydrocoumarin. This reaction is extremely rapid, even when the electrophile is an amide and the leaving group is an amino group of a small-molecule drug, fluorophore, peptide, or nucleic acid. O -Acylation of the phenolic hydroxyl group prevents reaction, providing a trigger for the reaction. Thus, the release of an amino group from an amide can be coupled to the hydrolysis of a designated ester (or to another chemical reaction that regenerates the hydroxyl group). Trimethyl lock conjugates are easy to synthesize, making the trimethyl lock a highly versatile module for chemical biology and related fields. The trimethyl lock provides unmatched attributes as a trigger for the release of small molecules by an enzymatic, chemical, or photolytic process.</abstract><cop>England</cop><pmid>23181187</pmid><doi>10.1039/c2sc20536j</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 2041-6520
ispartof Chemical science (Cambridge), 2012-01, Vol.3 (8), p.2412-242
issn 2041-6520
2041-6539
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3501758
source Royal Society of Chemistry
title Trimethyl lock: a trigger for molecular release in chemistry, biology, and pharmacology
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-28T15%3A03%3A19IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmed_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Trimethyl%20lock:%20a%20trigger%20for%20molecular%20release%20in%20chemistry,%20biology,%20and%20pharmacology&rft.jtitle=Chemical%20science%20(Cambridge)&rft.au=Levine,%20Michael%20N&rft.date=2012-01-01&rft.volume=3&rft.issue=8&rft.spage=2412&rft.epage=242&rft.pages=2412-242&rft.issn=2041-6520&rft.eissn=2041-6539&rft_id=info:doi/10.1039/c2sc20536j&rft_dat=%3Cpubmed_cross%3E23181187%3C/pubmed_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c492t-c53c547b6f0c513fc474e566f4cbb595e1b7793ee4de178b9f2751d401d610f93%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_id=info:pmid/23181187&rfr_iscdi=true