Somasekhar Bondalapati - Academia.edu (original) (raw)
Papers by Somasekhar Bondalapati
Nature Chemistry, 2016
O ver 100 years have passed since the first attempts to form amide bonds using simple starting ma... more O ver 100 years have passed since the first attempts to form amide bonds using simple starting materials. Despite this, great efforts are still being invested to develop new methods of efficiently forming amide bonds at low cost using environmentally friendly reagents 1. Synthesis of short peptide sequences (20-40 amino acids (AA)) is considered a relatively straightforward process with some exceptions such as amyloid β-peptides, transmembrane peptides and amphiphilic peptides. These difficult peptide sequences require special coupling reagents and synthetic strategies to achieve efficient synthesis. The relative ease by which essentially any short tailored peptide can be synthesized by applying solid-phase peptide synthesis (SPPS) has arisen from the continuous development of a wide variety of excellent coupling reagents, resins with better physical properties, novel linkers and orthogonal protecting groups 2. Improvement in chromatographic methods and analytical instrumentation for purification and characterization has also simplified the process of synthesizing peptides. The high efficiency of peptide synthesis coupled with automation has greatly expanded the use of peptides in several research areas, such as nanotechnology, drug discovery and total chemical synthesis of proteins. Chemical protein synthesis, which relies on chemoselective peptide ligation methods, such as native chemical ligation (NCL) 3 , offers complete control of the atomic composition of the polypeptide sequence, making it advantageous over molecular biology approaches in some areas of research (Fig. 1) 4. For example, it enables the incorporation of post-translational modifications (PTMs) into proteins with high homogeneity and in usable quantities, which can enable the role of these modifications on the protein structure and function to be examined. This method for the production of posttranslationally modified proteins has generated immense interests among many groups who have prepared, for example, glycosylated, phosphorylated and ubiquitinated proteins that have enabled otherwise difficult studies 5. Another exciting aspect of chemical protein synthesis is the ability to prepare mirror-image proteins, which are increasingly finding impressive applications in drug discovery 6 and protein crystallography 7 .
Chemistry (Weinheim an der Bergstrasse, Germany), 2015
Modification of ubiquitin by phosphorylation extends the signaling possibilities of this dynamic ... more Modification of ubiquitin by phosphorylation extends the signaling possibilities of this dynamic signal, as it could affect the activity of ligases and the processing of ubiquitin chains by deubiquitinases. The first chemical synthesis of phosphorylated ubiquitin and of Lys63-linked diubiquitin at the proximal, distal or both ubiquitins is reported. This enabled the examination of how such a modification alters E1-E2 activities of the ubiquitination machinery. It is found that E1 charging was not affected, while the assembly of phosphorylated ubiquitin chains was differentially inhibited with E2 enzymes tested. Moreover, this study shows that phosphorylation interferes with the recognition of linkage specific antibodies and the activities of several deubiquitinases. Notably, phosphorylation in the proximal or distal ubiquitin unit has differential effects on specific deubiquitinases. These results support a unique role of phosphorylation in the dynamics of the ubiquitin signal.
Macromolecular Rapid Communications, 2014
![Research paper thumbnail of ChemInform Abstract: Synthesis of 2,3-Dihydro-4-pyranones from Epoxides via Intermolecular [4 + 2] Cycloaddition Reaction](https://attachments.academia-assets.com/93071272/thumbnails/1.jpg)
](ChemInform, 2013
Synthesis of 2,3-Dihydro-4-pyranones from Epoxides via Intermolecular [4 + 2] Cycloaddition React... more Synthesis of 2,3-Dihydro-4-pyranones from Epoxides via Intermolecular [4 + 2] Cycloaddition Reaction.-The title reaction can be applied to various epoxides and cyclobutanones. If diastereomeric product mixtures arise, the trans isomer is formed in excess.
Organic Letters, 2014
A strategy for the synthesis of dehydroalanine based diubiquitin activity probes is described. Th... more A strategy for the synthesis of dehydroalanine based diubiquitin activity probes is described. The site-specific introduction of dehydroalanine was achieved from diubiquitin bearing Cys residue near the scissile bond between two ubiquitins linked through Lys48, Lys63 or in a head to tail fashion. The probes were characterized for their activities with various deubiquitinases, which open new opportunities in studying deubiquitinases in various settings.
![Research paper thumbnail of A Novel Synthesis of Oxabicyclo[3.3.1]nonanone via (3,5)-Oxonium−Ene Reaction](https://attachments.academia-assets.com/93071279/thumbnails/1.jpg)
](Organic Letters, 2010
Oxabicyclo[3.3.1]nonanone can conveniently be prepared by the reaction of trans-p-menth-6-ene-2,8... more Oxabicyclo[3.3.1]nonanone can conveniently be prepared by the reaction of trans-p-menth-6-ene-2,8-diol and aldehyde or epoxide mediated by boron trifluoride etherate in good yields. The reaction proceeds via (3,5)-oxonium-ene-type reaction.
Journal of the American Chemical Society, 2014
Ubiquitination is one of the most ubiquitous posttranslational modifications in eukaryotes and is... more Ubiquitination is one of the most ubiquitous posttranslational modifications in eukaryotes and is involved in various cellular events such as proteasomal degradation and DNA repair. The overwhelming majority of studies aiming to understand ubiquitination and deubiquitination have employed unanchored ubiquitin chains and mono-ubiquitinated proteins. To shed light on these processes at the molecular level, it is crucial to have facile access to ubiquitin chains linked to protein substrates. Such conjugates are highly difficult to prepare homogenously and in workable quantities using the enzymatic machinery. To address this formidable challenge we developed new chemical approaches to covalently attach ubiquitin chains to a protein substrate through its Cys residue. A key aspect of this approach is the installation of acyl hydrazide functionality at the C-terminus of the proximal Ub, which allows, after ubiquitin chain assembly, the introduction of various reactive electrophiles for protein conjugation. Employing α-globin as a model substrate, we demonstrate the facile conjugation to K48-linked ubiquitin chains, bearing up to four ubiquitins, through disulfide and thioether linkages. These bioconjugates were examined for their behavior with the USP2 enzyme, which was found to cleave the ubiquitin chain in a similar manner to unanchored ones. Furthermore, proteasomal degradation study showed that di-ubiquitinated α-globin is rapidly degraded in contrast to the mono-ubiquitinated counterpart, highlighting the importance of the chain lengths on proteasomal degradation. The present work opens unprecedented opportunities in studying the ubiquitin signal by enabling access to site-specifically polyubiquitinated proteins with an increased size and complexity.
Journal of Fluorine Chemistry, 2010
Titanium tetrafluoride can efficiently be used for strereoselective synthesis of 4-fluorotetrahyd... more Titanium tetrafluoride can efficiently be used for strereoselective synthesis of 4-fluorotetrahydropyrans via Prins cyclization in good yields. The method is general and can be used for aldehydes as well as ketones.
Current Protocols in Chemical Biology, 2015
Chemical synthesis of complex biomolecules such as proteins is a challenging adventure, yet rewar... more Chemical synthesis of complex biomolecules such as proteins is a challenging adventure, yet rewarding in driving various biochemical and biophysical research activities. Over the years, the refinement of peptide synthesis and invention of ligation methodologies have led to the successful synthesis of several complex protein targets. Ubiquitin bioconjugates, which are being studied intensively by many groups due to their involvement in numerous biological processes, represent a fine example where chemistry is greatly aiding these studies. In this article, we describe the synthetic routes and strategies to prepare different ubiquitin analogs with desired modifications, as well as di-ubiquitin chains. © 2015 by John Wiley & Sons, Inc.
ChemInform, 2012
A three-component, one-pot synthesis of 4-aryltetrahydropyrans from epoxides and homoallylic alco... more A three-component, one-pot synthesis of 4-aryltetrahydropyrans from epoxides and homoallylic alcohols in arenes via Prins-Friedel-Crafts reaction, mediated by boron trifluoride etherate, has been developed. The reaction is diastereoselective and gives only all-cis diastereomers in moderate to good yields.
The Journal of organic chemistry, Jan 2, 2014
Intramolecular C−C bond formation of oxygen-and nitrogen-tethered alkynes and epoxide mediated by... more Intramolecular C−C bond formation of oxygen-and nitrogen-tethered alkynes and epoxide mediated by Lewis acid under ambient conditions is described. A simple procedure for the synthesis of 3,6-and 5,6-dihydropyrans and 3,4-dehydropiperidines from acyclic building blocks in good yields without using any transition metal is shown.
Tetrahedron Letters, 2012
A chiral 1,3-diol with a benzyl backbone has been used for the asymmetric oxidation of sulfides t... more A chiral 1,3-diol with a benzyl backbone has been used for the asymmetric oxidation of sulfides to sulfoxides. Moderate to good yields and enantioselectivity (upto 87% ee) have been observed.
ChemInform, 2012
A chiral 1,3-diol with a benzyl backbone has been used for the asymmetric oxidation of sulfides t... more A chiral 1,3-diol with a benzyl backbone has been used for the asymmetric oxidation of sulfides to sulfoxides. Moderate to good yields and enantioselectivity (upto 87% ee) have been observed.
European Journal of Organic Chemistry, 2013
Tetrahydroquinolines have been efficiently synthesized in good yields with excellent stereoselect... more Tetrahydroquinolines have been efficiently synthesized in good yields with excellent stereoselectivity. The reaction between α-allylic anilines and aldehydes proceeds through an [a] , 952-956 952 imino-ene cyclization that is mediated by boron trifluoridediethyl ether. Eur. J. Org. Chem. 2013, 952-956
European Journal of Medicinal Chemistry, 2013
The labdane diterpene, (E)-labda-8(17), 12-diene-15, 16-dial (compound A) and its epoxide analogu... more The labdane diterpene, (E)-labda-8(17), 12-diene-15, 16-dial (compound A) and its epoxide analogue, (E)-8b, 17-Epoxylabd-12-ene-15, 16-dial (compound B) were isolated from the seeds of Alpinia nigra for the first time. The antibacterial activities of both compounds were evaluated against three Gram-positive and four Gram-negative bacteria, and flow cytometric analysis revealed that these compounds caused significant damage to the bacterial cell membranes. Further, field emission scanning electron microscope imaging and cell leakage analysis confirmed that the labdane diterpenes were responsible for bacterial cell membrane damage and disintegration. Our findings provide new insight into the broad-spectrum effects of two natural labdane diterpenes that may be useful in the future development of herbal antibiotic products.
The Journal of Organic Chemistry, 2012
Substituted dihydropyrans can be efficiently synthesized in good yields with excellent diastereos... more Substituted dihydropyrans can be efficiently synthesized in good yields with excellent diastereoselectivity from the reaction of aldehydes or epoxides and ethyl 3-alkyl-3-hydroxy-5-methylhex-5-enoate via an oxonium-ene cyclization reaction catalyzed by trimethylsilyl trifluoromethanesulfonate (TMSOTf ) under mild conditions. † Electronic supplementary information (ESI) available: General experimental methods, copies of 1 H and 13 C NMR spectra of all compounds. See
Tetrahedron Letters, 2013
Scandium trifluoromethanesulfonate can efficiently catalyze the formation of homoallylic alcohols... more Scandium trifluoromethanesulfonate can efficiently catalyze the formation of homoallylic alcohols from olefins and paraformaldehyde in good yields.
Nature Chemistry, 2016
O ver 100 years have passed since the first attempts to form amide bonds using simple starting ma... more O ver 100 years have passed since the first attempts to form amide bonds using simple starting materials. Despite this, great efforts are still being invested to develop new methods of efficiently forming amide bonds at low cost using environmentally friendly reagents 1. Synthesis of short peptide sequences (20-40 amino acids (AA)) is considered a relatively straightforward process with some exceptions such as amyloid β-peptides, transmembrane peptides and amphiphilic peptides. These difficult peptide sequences require special coupling reagents and synthetic strategies to achieve efficient synthesis. The relative ease by which essentially any short tailored peptide can be synthesized by applying solid-phase peptide synthesis (SPPS) has arisen from the continuous development of a wide variety of excellent coupling reagents, resins with better physical properties, novel linkers and orthogonal protecting groups 2. Improvement in chromatographic methods and analytical instrumentation for purification and characterization has also simplified the process of synthesizing peptides. The high efficiency of peptide synthesis coupled with automation has greatly expanded the use of peptides in several research areas, such as nanotechnology, drug discovery and total chemical synthesis of proteins. Chemical protein synthesis, which relies on chemoselective peptide ligation methods, such as native chemical ligation (NCL) 3 , offers complete control of the atomic composition of the polypeptide sequence, making it advantageous over molecular biology approaches in some areas of research (Fig. 1) 4. For example, it enables the incorporation of post-translational modifications (PTMs) into proteins with high homogeneity and in usable quantities, which can enable the role of these modifications on the protein structure and function to be examined. This method for the production of posttranslationally modified proteins has generated immense interests among many groups who have prepared, for example, glycosylated, phosphorylated and ubiquitinated proteins that have enabled otherwise difficult studies 5. Another exciting aspect of chemical protein synthesis is the ability to prepare mirror-image proteins, which are increasingly finding impressive applications in drug discovery 6 and protein crystallography 7 .
Chemistry (Weinheim an der Bergstrasse, Germany), 2015
Modification of ubiquitin by phosphorylation extends the signaling possibilities of this dynamic ... more Modification of ubiquitin by phosphorylation extends the signaling possibilities of this dynamic signal, as it could affect the activity of ligases and the processing of ubiquitin chains by deubiquitinases. The first chemical synthesis of phosphorylated ubiquitin and of Lys63-linked diubiquitin at the proximal, distal or both ubiquitins is reported. This enabled the examination of how such a modification alters E1-E2 activities of the ubiquitination machinery. It is found that E1 charging was not affected, while the assembly of phosphorylated ubiquitin chains was differentially inhibited with E2 enzymes tested. Moreover, this study shows that phosphorylation interferes with the recognition of linkage specific antibodies and the activities of several deubiquitinases. Notably, phosphorylation in the proximal or distal ubiquitin unit has differential effects on specific deubiquitinases. These results support a unique role of phosphorylation in the dynamics of the ubiquitin signal.
Macromolecular Rapid Communications, 2014
ChemInform, 2013
Synthesis of 2,3-Dihydro-4-pyranones from Epoxides via Intermolecular [4 + 2] Cycloaddition React... more Synthesis of 2,3-Dihydro-4-pyranones from Epoxides via Intermolecular [4 + 2] Cycloaddition Reaction.-The title reaction can be applied to various epoxides and cyclobutanones. If diastereomeric product mixtures arise, the trans isomer is formed in excess.
Organic Letters, 2014
A strategy for the synthesis of dehydroalanine based diubiquitin activity probes is described. Th... more A strategy for the synthesis of dehydroalanine based diubiquitin activity probes is described. The site-specific introduction of dehydroalanine was achieved from diubiquitin bearing Cys residue near the scissile bond between two ubiquitins linked through Lys48, Lys63 or in a head to tail fashion. The probes were characterized for their activities with various deubiquitinases, which open new opportunities in studying deubiquitinases in various settings.
Organic Letters, 2010
Oxabicyclo[3.3.1]nonanone can conveniently be prepared by the reaction of trans-p-menth-6-ene-2,8... more Oxabicyclo[3.3.1]nonanone can conveniently be prepared by the reaction of trans-p-menth-6-ene-2,8-diol and aldehyde or epoxide mediated by boron trifluoride etherate in good yields. The reaction proceeds via (3,5)-oxonium-ene-type reaction.
Journal of the American Chemical Society, 2014
Ubiquitination is one of the most ubiquitous posttranslational modifications in eukaryotes and is... more Ubiquitination is one of the most ubiquitous posttranslational modifications in eukaryotes and is involved in various cellular events such as proteasomal degradation and DNA repair. The overwhelming majority of studies aiming to understand ubiquitination and deubiquitination have employed unanchored ubiquitin chains and mono-ubiquitinated proteins. To shed light on these processes at the molecular level, it is crucial to have facile access to ubiquitin chains linked to protein substrates. Such conjugates are highly difficult to prepare homogenously and in workable quantities using the enzymatic machinery. To address this formidable challenge we developed new chemical approaches to covalently attach ubiquitin chains to a protein substrate through its Cys residue. A key aspect of this approach is the installation of acyl hydrazide functionality at the C-terminus of the proximal Ub, which allows, after ubiquitin chain assembly, the introduction of various reactive electrophiles for protein conjugation. Employing α-globin as a model substrate, we demonstrate the facile conjugation to K48-linked ubiquitin chains, bearing up to four ubiquitins, through disulfide and thioether linkages. These bioconjugates were examined for their behavior with the USP2 enzyme, which was found to cleave the ubiquitin chain in a similar manner to unanchored ones. Furthermore, proteasomal degradation study showed that di-ubiquitinated α-globin is rapidly degraded in contrast to the mono-ubiquitinated counterpart, highlighting the importance of the chain lengths on proteasomal degradation. The present work opens unprecedented opportunities in studying the ubiquitin signal by enabling access to site-specifically polyubiquitinated proteins with an increased size and complexity.
Journal of Fluorine Chemistry, 2010
Titanium tetrafluoride can efficiently be used for strereoselective synthesis of 4-fluorotetrahyd... more Titanium tetrafluoride can efficiently be used for strereoselective synthesis of 4-fluorotetrahydropyrans via Prins cyclization in good yields. The method is general and can be used for aldehydes as well as ketones.
Current Protocols in Chemical Biology, 2015
Chemical synthesis of complex biomolecules such as proteins is a challenging adventure, yet rewar... more Chemical synthesis of complex biomolecules such as proteins is a challenging adventure, yet rewarding in driving various biochemical and biophysical research activities. Over the years, the refinement of peptide synthesis and invention of ligation methodologies have led to the successful synthesis of several complex protein targets. Ubiquitin bioconjugates, which are being studied intensively by many groups due to their involvement in numerous biological processes, represent a fine example where chemistry is greatly aiding these studies. In this article, we describe the synthetic routes and strategies to prepare different ubiquitin analogs with desired modifications, as well as di-ubiquitin chains. © 2015 by John Wiley & Sons, Inc.
ChemInform, 2012
A three-component, one-pot synthesis of 4-aryltetrahydropyrans from epoxides and homoallylic alco... more A three-component, one-pot synthesis of 4-aryltetrahydropyrans from epoxides and homoallylic alcohols in arenes via Prins-Friedel-Crafts reaction, mediated by boron trifluoride etherate, has been developed. The reaction is diastereoselective and gives only all-cis diastereomers in moderate to good yields.
The Journal of organic chemistry, Jan 2, 2014
Intramolecular C−C bond formation of oxygen-and nitrogen-tethered alkynes and epoxide mediated by... more Intramolecular C−C bond formation of oxygen-and nitrogen-tethered alkynes and epoxide mediated by Lewis acid under ambient conditions is described. A simple procedure for the synthesis of 3,6-and 5,6-dihydropyrans and 3,4-dehydropiperidines from acyclic building blocks in good yields without using any transition metal is shown.
Tetrahedron Letters, 2012
A chiral 1,3-diol with a benzyl backbone has been used for the asymmetric oxidation of sulfides t... more A chiral 1,3-diol with a benzyl backbone has been used for the asymmetric oxidation of sulfides to sulfoxides. Moderate to good yields and enantioselectivity (upto 87% ee) have been observed.
ChemInform, 2012
A chiral 1,3-diol with a benzyl backbone has been used for the asymmetric oxidation of sulfides t... more A chiral 1,3-diol with a benzyl backbone has been used for the asymmetric oxidation of sulfides to sulfoxides. Moderate to good yields and enantioselectivity (upto 87% ee) have been observed.
European Journal of Organic Chemistry, 2013
Tetrahydroquinolines have been efficiently synthesized in good yields with excellent stereoselect... more Tetrahydroquinolines have been efficiently synthesized in good yields with excellent stereoselectivity. The reaction between α-allylic anilines and aldehydes proceeds through an [a] , 952-956 952 imino-ene cyclization that is mediated by boron trifluoridediethyl ether. Eur. J. Org. Chem. 2013, 952-956
European Journal of Medicinal Chemistry, 2013
The labdane diterpene, (E)-labda-8(17), 12-diene-15, 16-dial (compound A) and its epoxide analogu... more The labdane diterpene, (E)-labda-8(17), 12-diene-15, 16-dial (compound A) and its epoxide analogue, (E)-8b, 17-Epoxylabd-12-ene-15, 16-dial (compound B) were isolated from the seeds of Alpinia nigra for the first time. The antibacterial activities of both compounds were evaluated against three Gram-positive and four Gram-negative bacteria, and flow cytometric analysis revealed that these compounds caused significant damage to the bacterial cell membranes. Further, field emission scanning electron microscope imaging and cell leakage analysis confirmed that the labdane diterpenes were responsible for bacterial cell membrane damage and disintegration. Our findings provide new insight into the broad-spectrum effects of two natural labdane diterpenes that may be useful in the future development of herbal antibiotic products.
The Journal of Organic Chemistry, 2012
Substituted dihydropyrans can be efficiently synthesized in good yields with excellent diastereos... more Substituted dihydropyrans can be efficiently synthesized in good yields with excellent diastereoselectivity from the reaction of aldehydes or epoxides and ethyl 3-alkyl-3-hydroxy-5-methylhex-5-enoate via an oxonium-ene cyclization reaction catalyzed by trimethylsilyl trifluoromethanesulfonate (TMSOTf ) under mild conditions. † Electronic supplementary information (ESI) available: General experimental methods, copies of 1 H and 13 C NMR spectra of all compounds. See
Tetrahedron Letters, 2013
Scandium trifluoromethanesulfonate can efficiently catalyze the formation of homoallylic alcohols... more Scandium trifluoromethanesulfonate can efficiently catalyze the formation of homoallylic alcohols from olefins and paraformaldehyde in good yields.