Exploring the scope of DBU-promoted amidations of 7-carboxymethyl-pterin

Pteridines are an important heterocycle often used in the development of pharmaceutically relevant compounds, and in the field of supramolecular chemistry. Their synthetic use is often hampered by the notorious insolubility of pterins, slowing the development of novel pteridine derivatives. Reactions which expedite the rapid development of new pterins are thus of great importance. Through a dual role of diazabicycloundecene (DBU), 7-carboxymethyl-pterin is converted to the soluble DBU salt, with additional DBU promoting an ester-to-amide transformation. We have explored this reaction to assess its scope and identify structural features in the amines which significantly affect success, monitored the reaction using pseudo-first order kinetics, and further adapted the reaction conditions to allow for product formation in as little as 5 min, with yields often \u3e80%

Exploring the scope of DBU-promoted amidations of 7-carboxymethyl-pterin

Pteridines are an important heterocycle often used in the development of pharmaceutically relevant compounds, and in the field of supramolecular chemistry. Their synthetic use is often hampered by the notorious insolubility of pterins, slowing the development of novel pteridine derivatives. Reactions which expedite the rapid development of new pterins are thus of great importance. Through a dual role of diazabicycloundecene (DBU), 7-carboxymethyl-pterin is converted to the soluble DBU salt, with additional DBU promoting an ester-to-amide transformation. We have explored this reaction to assess its scope and identify structural features in the amines which significantly affect success, monitored the reaction using pseudo-first order kinetics, and further adapted the reaction conditions to allow for product formation in as little as 5 min, with yields often \u3e80%

Synthetic Routes to a Library of Novel Methionine Synthase Inhibitors

Fungal infections are of continuous concern, especially with regard to immunocompromised patients. In an effort to develop new potential anti-fungal agents, we have begun synthesizing a library of potential inhibitors of the fungal Methionine Synthase (MetSyn) enzyme. Key differences between the B12-independant fungal MetSyn enzyme and the B12-dependant mammalian form can allow for an antifungal drug to be developed to exclusively bind the fungal enzyme and inhibit fungal growth while leaving the host (patient) unaffected. We are currently exploring the synthesis of various pterin and deazaguanine-based molecules as these mimic folate, an essential substrate for MetSyn function. We have begun testing these new molecules for activity in a fungal growth assay, as well as a fluorescent assay for monitoring MetSyn activity

Synthetic Routes to a Library of Novel Methionine Synthase Inhibitors

Fungal infections are of continuous concern, especially with regard to immunocompromised patients. In an effort to develop new potential anti-fungal agents, we have begun synthesizing a library of potential inhibitors of the fungal Methionine Synthase (MetSyn) enzyme. Key differences between the B12-independant fungal MetSyn enzyme and the B12-dependant mammalian form can allow for an antifungal drug to be developed to exclusively bind the fungal enzyme and inhibit fungal growth while leaving the host (patient) unaffected. We are currently exploring the synthesis of various pterin and deazaguanine-based molecules as these mimic folate, an essential substrate for MetSyn function. We have begun testing these new molecules for activity in a fungal growth assay, as well as a fluorescent assay for monitoring MetSyn activity

Mondialisation formation et développement dans les pays du Nord et du Sud

Dans un contexte de mondialisation, où l’économie, les évolutions politiques et socioculturelles jouent un rôle déterminant, les pratiques de formation des enseignants doivent être renouvelées pour répondre aux attentes de la société et en faisant une part importante à la professionnalisation.In the context of globalisation, in which the economy and political and socio-cultural changes play a major part, practises in teacher training must be renewed to respond to what society expects, insisting more particularly on professionalisation.En un contexto de mundialización, en el que la economia, las evolu-ciones politicas y socioculturales desempenan un papel determinante, las prâcticas de formación de los docentes deben renovarse para responder a las esperas de la sociedad otorgándole un lugar importante a la profesionalización

Progress Towards a Library of Potential Fungicides

Methionine Synthase (MetSyn) is an enzyme that uses folate and homocysteine to create the amino acid methionine, which is essential for all organisms. There are key differences between the fungal MetSyn enzyme and the mammalian (human) form, especially with regard to the proximity of the two binding sites for folate and homocysteine. Taking advantage of these differences, an antifungal drug could be developed to exclusively bind the fungal enzyme and inhibit fungal growth while leaving the host (patient) unaffected. We are currently exploring the synthesis of various molecules that mimic folate, an essential substrate for MetSyn function. We plan to screen these molecules against a multitude of fungal species as well as in an isolated system with the MetSyn enzyme itself

Streamlining the synthesis of folate mimics as potential antifungal agents

Methionine Synthase (MetSyn) is an enzyme that creates the amino acid methionine, which is essential for all organisms. There are key differences between the B12-independent fungal MetSyn enzyme and the B12-dependant mammalian form, especially with regard to the proximity of the two active sites. Taking advantage of these differences, an antifungal drug could be developed to exclusively bind the fungal enzyme and inhibit fungal growth while leaving the host (patient) unaffected. As MetSyn is a folate-dependent enzyme, we are currently exploring the synthesis of various pterin-based molecules as these mimic the essential folate substrate. We have developed optimized paths to allow for rapid generation of new folate-mimics and other pterin derivatives. We have expressed the MetSyn enzyme and begun testing these molecules for activity in a fluorescent assay for monitoring MetSyn activity

Streamlining the synthesis of folate mimics as potential antifungal agents

Methionine Synthase (MetSyn) is an enzyme that creates the amino acid methionine, which is essential for all organisms. There are key differences between the B12-independent fungal MetSyn enzyme and the B12-dependant mammalian form, especially with regard to the proximity of the two active sites. Taking advantage of these differences, an antifungal drug could be developed to exclusively bind the fungal enzyme and inhibit fungal growth while leaving the host (patient) unaffected. As MetSyn is a folate-dependent enzyme, we are currently exploring the synthesis of various pterin-based molecules as these mimic the essential folate substrate. We have developed optimized paths to allow for rapid generation of new folate-mimics and other pterin derivatives. We have expressed the MetSyn enzyme and begun testing these molecules for activity in a fluorescent assay for monitoring MetSyn activity

Progress Towards a Library of Potential Fungicides

Methionine Synthase (MetSyn) is an enzyme that uses folate and homocysteine to create the amino acid methionine, which is essential for all organisms. There are key differences between the fungal MetSyn enzyme and the mammalian (human) form, especially with regard to the proximity of the two binding sites for folate and homocysteine. Taking advantage of these differences, an antifungal drug could be developed to exclusively bind the fungal enzyme and inhibit fungal growth while leaving the host (patient) unaffected. We are currently exploring the synthesis of various molecules that mimic folate, an essential substrate for MetSyn function. We plan to screen these molecules against a multitude of fungal species as well as in an isolated system with the MetSyn enzyme itself