A class of inhibitors of mitogen activated protein kinase-activated kinase 2 (MK2) was discovered via high-throughput screening. This compound class demonstrates activity against the enzyme with sub-microM IC(50) values, and suppresses LPS-induced TNFalpha levels in THP-1 cells. MK2 inhibition kinetic measurements indicated mixed binding approaching non-ATP competitive inhibition.

Design principles and syntheses of three haptens that were recently reported to generate amide bond cleaving catalytic antibodies are described. The hapten designs sought to induce acidic and/or basic residues in antibody binding sites via charge complementarity, and also to generate a hydrophobic binding pocket for an external phenol nucleophile. The charged yet aromatic nature of these haptens presented some unique synthetic challenges and solutions to which are described below.

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTAntibody Catalyzed Cleavage of an Amide Bond Using an External Nucleophilic CofactorOguz Ersoy, Roman Fleck, Anthony Sinskey, and Satoru MasamuneView Author Information Departments of Chemistry and Biology Massachusetts Institute of Technology Cambridge, Massachusetts 02139 Cite this: J. Am. Chem. Soc. 1998, 120, 4, 817–818Publication Date (Web):January 14, 1998Publication History Received16 September 1997Published online14 January 1998Published inissue 1 February 1998https://pubs.acs.org/doi/10.1021/ja9732542https://doi.org/10.1021/ja9732542rapid-communicationACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views203Altmetric-Citations17LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Amides,Aromatic compounds,Biopolymers,Immunology,Peptides and proteins Get e-Alerts

Human antibodies against HIV-1 have been sought to study neutralization events on the molecular level, and for possible use in passive immune intervention. The development of phage display techniques has opened the possibility of rapidly generating human monoclonal antibodies with desired specificities. We and others have isolated human HIV-1 neutralizing antibody fragments using this technique. Bacterial expression of isolated clones does, however, differ broadly both in expression levels and functional activity. In addition, intact IgG cannot be expressed in bacteria. By transferring the genes of isolated Fab clones to a mammalian expression system we could perform a comparison of functional activity between Fab expressed in bacterial and mammalian cells, as well as Fab and whole IgG. Fab fragments expressed in mammalian cells showed increased virus neutralizing activity compared to the same Fab clones expressed in Escherichia coli, underlining the inefficiency of procaryotic expression. No difference in HIV-1 neutralizing capacity was detected between monovalent (Fab) and divalent (whole antibody) reagents expressed in CHO cells. Thus, bivalency does not always confer improved neutralization efficacy.

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTN → O Acyl-Transfer Reaction Catalyzed by AntibodiesOguz Ersoy, Roman Fleck, Anthony Sinskey, and Satoru MasamuneView Author Information Departments of Chemistry and Biology Massachusetts Institute of Technology Cambridge, Massachusetts 02139 Cite this: J. Am. Chem. Soc. 1996, 118, 51, 13077–13078Publication Date (Web):December 25, 1996Publication History Received28 August 1996Published online25 December 1996Published inissue 1 January 1996https://doi.org/10.1021/ja963026sCopyright © 1996 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views151Altmetric-Citations14LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (85 KB) Get e-AlertsSUBJECTS:Amides,Biopolymers,Hydrolysis,Immunology,Peptides and proteins Get e-Alerts

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCatalytic antibodies generated via heterologous immunizationHiroaki Suga, Oguz Ersoy, Simon F. Williams, Takeshi Tsumuraya, Michael N. Margolies, Anthony J. Sinskey, and Satoru MasamuneCite this: J. Am. Chem. Soc. 1994, 116, 13, 6025–6026Publication Date (Print):June 1, 1994Publication History Published online1 May 2002Published inissue 1 June 1994https://pubs.acs.org/doi/10.1021/ja00092a086https://doi.org/10.1021/ja00092a086research-articleACS PublicationsRequest reuse permissionsArticle Views126Altmetric-Citations28LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts

Three structurally related haptens 1-3 were designed and synthesized with the goal of generating antibodies for the hydrolysis of ester 4a and amide 4b. These haptens contain a 1,2-amino alcohol functionality which replaces the ester/amide moiety of the substrates. A number of catalytic antibodies were generated, and the Michaelis-Menten kinetics constants of three representative catalytic antibodies induced to each of haptens 1-3 were determined. These catalytic antibodies accelerated the hydrolysis of ester 4a with k(cat)/k(un) = approximately 3 X 10(3), and their catalytic activities were effectively inhibited by the addition of their respective haptens. To evaluate the structural influences of the hapten on antibody binding and specificity as well as catalytic activity, a total of 18 antibodies including the above catalytic antibodies and three representative noncatalytic antibodies from each group were selected, and their dissociation constants with their respective haptens, amide 4b, and products were determined. The studies have shown that (1) the structural variations among the three haptens induce no significant changes in catalytic activity of antibodies while they slightly influence the antibody binding and specificity for the substrate and products and (2) a high probability (reaching nearly 50%) of finding catalytic activity among the monoclonal antibodies raised to hapten 1 is found, suggesting that the induction of a charged complementary amino acid residue in close proximity to the reaction site may be important to generation of catalytic antibodies.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCatalytic antibodies generated via heterologous immunization. [Erratum to document cited in CA121:80587]Hiroaki Suga, Oguz Ersoy, Simon F. Williams, Takeshi Tsumuraya, Michael N. Margolies, Anthony J. Sinskey, and Satoru MasamuneCite this: J. Am. Chem. Soc. 1994, 116, 18, 8432Publication Date (Print):September 1, 1994Publication History Published online1 May 2002Published inissue 1 September 1994https://doi.org/10.1021/ja00097a087RIGHTS & PERMISSIONSArticle Views44Altmetric-Citations3LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (94 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts