Papers by Kiran Singarapu
Biochemistry, 2011
Vitamin D receptor (VDR) is a member of the nuclear hormone receptor superfamily. When bound to a... more Vitamin D receptor (VDR) is a member of the nuclear hormone receptor superfamily. When bound to a variety of vitamin D analogues, VDR manifests a wide diversity of physiological actions. The molecular mechanism by which different vitamin D analogues cause specific responses is not understood. The published crystallographic structures of the ligand binding domain of VDR (VDR-LBD) complexed with ligands that have differential biological activities have exhibited identical protein conformations. Here we report that rat VDR-LBD (rVDR-LBD) in solution exhibits differential chemical shifts when bound to three ligands that cause diverse responses: the natural hormone, 1,25dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ], a potent agonist analogue, 2-methylene-19-nor-(20S)-1,25dihydroxyvitamin D 3 [2MD], and an antagonist, 2-methylene-(22E)-(24R)-25-carbobutoxy-26,27-cyclo-22-dehydro-1α,24-dihydroxy-19-norvitamin D 3 [OU-72]. Ligand-specific chemical shifts mapped not only to residues at or near the binding pocket but also to residues remote from the ligand binding site. The complexes of rVDR-LBD with native hormone and the potent agonist 2MD exhibited chemical shift differences in signals from helix-12, which is part of the AF2 transactivation domain that appears to play a role in the selective recruitment of coactivators. By contrast, formation of the complex of rVDR-LBD with the antagonist OU-72 led to disappearance of signals from residues in helices-11 and -12. We present evidence that disorder in this region of the receptor in the antagonist complex prevents the attachment of coactivators.
Chem. Commun., 2015
Phenacyl azides were reacted with pyridinium ylides in the presence of Cu(OAc)2 (2 mol%) and Et3N... more Phenacyl azides were reacted with pyridinium ylides in the presence of Cu(OAc)2 (2 mol%) and Et3N utilizing molecular oxygen as a green oxidant to yield imidazo[1,2-a]pyridines in exclusive regioselectivity. Following the optimized protocol, 28 different fused heterocycles were synthesized in high yields (71-92%). In order to get mechanistic insight into the reaction, a few control experiments were carried out and the role of the copper salt was discussed.
Biomolecular NMR Assignments, 2015
Methionine aminopeptidase Type I (MetAP1) cleaves the initiator methionine from about 70 % of all... more Methionine aminopeptidase Type I (MetAP1) cleaves the initiator methionine from about 70 % of all newly synthesized proteins in almost every living cell. Human MetAP1 is a two domain protein with a zinc finger on the N-terminus and a catalytic domain on the C-terminus. Here, we report the chemical shift assignments of the amino terminal zinc binding domain (ZBD) (1-83 residues) of the human MetAP1 derived by using advanced NMR spectroscopic methods. We were able to assign the chemical shifts of ZBD of MetAP1 nearly complete, which reveal two helical fragments involving residues P44-L49 (α1) and Q59-K82 (α2). The protein structure unfolds upon complex formation with the addition of 2 M excess EDTA, indicated by the appearance of amide resonances in the random coil chemical shift region of (15)NHSQC spectrum.
Org. Biomol. Chem., 2015
A domino reaction has been developed for the synthesis of oxygen bridged bicyclic ethers through ... more A domino reaction has been developed for the synthesis of oxygen bridged bicyclic ethers through the coupling of 4-(2-hydroxyethyl)cyclohex-3-enols with aldehydes in the presence of 10 mol% of molecular iodine in dichloromethane at 25 °C. This method is highly diastereoselective affording the corresponding bicyclic ethers, i.e. octahydro-4a,7-epoxyisochromenes in good yields with high selectivity. It is the first report on the synthesis of oxygen bridged bicyclic ethers using a domino Prins strategy.
European Journal of Organic Chemistry, 2015
ABSTRACT A Prins bicyclization strategy for the stereoselective synthesis of trans-fused hexahydr... more ABSTRACT A Prins bicyclization strategy for the stereoselective synthesis of trans-fused hexahydropyrano[3,4-c]chromene derivatives in good to excellent yields has been developed. The synthetic versatility of this approach has been demonstrated in the synthesis of calyxin I and J analogues. This is the first example of the synthesis of hexahydropyrano[3,4-c]chromene derivatives from (E)-3-[2-(benzyloxy)phenyl]-5-phenylpent-4-en-1-ol (4b) and aldehydes.
ChemInform, 2015
ABSTRACT An efficient approach for the construction of novel bicyclic fused cyclopentenones start... more ABSTRACT An efficient approach for the construction of novel bicyclic fused cyclopentenones starting from Morita-Baylis-Hillman (MBH) acetates of acetylenic aldehydes with flexible scaffold diversity has been achieved using two-step reaction sequence involving allylic substitution and Pauson-Khand reaction. This strategy provided a facile access to various bicyclic cyclopentenones fused either with carbocyclic or heterocyclic ring system in good yield.
Tetrahedron Letters, 2002
The combination of homo-phenylglycine (Hpg) and proline leads to the formation of a b-turn mimic,... more The combination of homo-phenylglycine (Hpg) and proline leads to the formation of a b-turn mimic, which can be transformed into a cyclic peptide using a ring closing metathesis reaction. The presence of the pentenoyl and allyl groups at the terminus of the peptide leads to the concomitant formation of a linker surrogate fourth amino acid (6-amino-4-hexenoic acid; Aha) during the cyclization. The cyclic peptide is unique in having a pseudo 3 10 helical structure.
The Journal of Organic Chemistry, 2014
ChemInform, 2002
Sc(OTf ) 3 -Catalyzed Synthesis of Pyrano[3,2-b]-1-benzopyrans from D-Glycals. -In the presence o... more Sc(OTf ) 3 -Catalyzed Synthesis of Pyrano[3,2-b]-1-benzopyrans from D-Glycals. -In the presence of catalytic amounts of scandium triflate o-hydroxyaldehydes, D-glycals and trimethyl orthoformate react smoothly to give cis-anellated pyranobenzopyrans (IV) in good yields and diastereoselectivity. -(YADAV, J. S.; REDDY, B. V. S.; CHANDRAIAH, L.; JAGANNADH, B.; KUMAR, S.
Tetrahedron Letters, 2014
ABSTRACT A novel intramolecular Prins cyclization of (E)-5-(2-(hydroxymethyl)phenyl)pent-4-en-1-o... more ABSTRACT A novel intramolecular Prins cyclization of (E)-5-(2-(hydroxymethyl)phenyl)pent-4-en-1-ol with aldehydes has been achieved using 10 mol % BF3 center dot Et2O to produce 1-(tetrahydropyran-3-yl)-1,3-dihydroisobenzofuran derivatives in good to excellent yields with high selectivity. Similar type of coupling with salicylaldehydes provides the trans-fused hexahydropyrano[3,2-c]chromene derivatives in excellent yields. (C) 2014 Published by Elsevier Ltd.
Tetrahedron Letters, 2005
Conformational analysis of peptides containing a glucose-derived furanoid sugar amino acid (Gaa) ... more Conformational analysis of peptides containing a glucose-derived furanoid sugar amino acid (Gaa) by detailed NMR and constrained MD studies revealed that peptides with repeating Gaa-Leu-Val units had conformational signatures very similar to those of linear homooligomers of Gaa.
RSC Advances, 2014
Efficient regio-and stereoselective synthesis of novel of spiropyrrolidines was achieved through ... more Efficient regio-and stereoselective synthesis of novel of spiropyrrolidines was achieved through 1,3-dipolar cycloaddition reaction of 2-styrylquinazolin-4(3H)-ones with azomethine ylides generated in situ from decarboxylative coupling of L-proline and isatin. The present approach offers the advantages of a clean and simple methodology, high atom economy, short reaction time, wide substrate scope, and a high yielding protocol for spiropyrrolidines.
ChemInform, 2005
Conditions. -A rapid and efficient synthesis of title compounds is achieved from 2-formyl glycals... more Conditions. -A rapid and efficient synthesis of title compounds is achieved from 2-formyl glycals (I) and hydrazines. Under solvent-free microwave conditions improved yields are obtained compared to conventional heating. -(YADAV*, J. S.; REDDY, B. V. S.; SATHEESH, G.; LAKSHMI, P. N.; KUMAR, S. K.; KUNWAR, A. C.; Tetrahedron Lett. 45 (2004) 46, 8587-8590; Div. Org. Chem., Indian Inst. Chem. Technol., Hyderabad 500 007, India; Eng.) -Mais 08-121
Tetrahedron, 2004
Vasoactive intestinal peptide (VIP) is a widely distributed naturally occurring neuropeptide cont... more Vasoactive intestinal peptide (VIP) is a widely distributed naturally occurring neuropeptide containing 28 amino acids with wide ranging biological activities. 1 It has been found that VIP receptors are over-expressed on a variety of malignant tumor cells that are also associated with the ...
European Journal of Organic Chemistry, 2014
A Prins cascade process was developed for the synthesis of tetrahydro-3H-spiro[isobenzofuran-pyra... more A Prins cascade process was developed for the synthesis of tetrahydro-3H-spiro[isobenzofuran-pyran] derivatives in good yields and selectivity by the condensation of 3-[2-(hydroxymethyl)phenyl]but-3-en-1-ols with aldehydes or ketones. The reaction proceeds smoothly in the presence of indium(III) triwww.eurjoc.org
The Journal of Physical Chemistry B, 2009
Determination of DNA solution structure is a difficult task even with the high-sensitivity method... more Determination of DNA solution structure is a difficult task even with the high-sensitivity method used here based on simulated annealing with 35 restraints/residue (cryoprobe 750 MHz NMR).
Tetrahedron Letters, 2002
A novel 18-membered cyclic oligopeptide 1 based on 5-(aminomethyl)-2-furancarboxylic acid (2), is... more A novel 18-membered cyclic oligopeptide 1 based on 5-(aminomethyl)-2-furancarboxylic acid (2), is developed as an excellent receptor for carboxylate binding having an association constant of 8.64×10 3 M −1 for tetrabutylammonium acetate in CD 3 CN. The synthesis of 1 was achieved by a high-yielding cyclotrimerization reaction of the unfunctionalized furan amino acid 2.
Tetrahedron Letters, 2002
The products 2 and 3 were easily separated on silica gel column chromatography. Interestingly, th... more The products 2 and 3 were easily separated on silica gel column chromatography. Interestingly, the reaction of 3,4,6-tri-O-benzyl or methyl or allyl-d-glucal with furan or pyrrole gave exclusively C-3-adducts 2 without the formation of 3 under the reaction conditions. ...
Tetrahedron Letters, 2002
A new peptidomimetic scaffold based on 5-(aminomethyl)pyrrole-2-carboxylic acid is developed for ... more A new peptidomimetic scaffold based on 5-(aminomethyl)pyrrole-2-carboxylic acid is developed for the first time and used as a conformationally constrained surrogate of the Gly-DAla dipeptide isostere (2) to prepare peptides 3 and 4.
Tetrahedron Letters, 2003
Designed b-hairpin peptides tolerate insertion of 3-amino benzoic acid (3-Aba) and also permit ac... more Designed b-hairpin peptides tolerate insertion of 3-amino benzoic acid (3-Aba) and also permit accommodation of both enantiomers of Pro-Gly turn motifs.
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Papers by Kiran Singarapu