Papers by Tuomas Karskela
EJNMMI radiopharmacy and chemistry, Feb 23, 2024
Planta medica international open, Oct 1, 2017
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Organic and Biomolecular Chemistry, 2006
A method for solid-supported synthesis of N,N-disubstituted (3H-imidazo[2,1-i]purin-7-yl)methyl a... more A method for solid-supported synthesis of N,N-disubstituted (3H-imidazo[2,1-i]purin-7-yl)methyl amines has been developed. The key features of this library synthesis are: (i) immobilization of commercially available N6-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-deoxyadenosine 3'-(2-cyanoethyl N,N-diisopropylphosphoramidite) by phosphitylation to a hydroxyl-functionalized support, (ii) quantitative conversion of the deprotected adenine base to 3H-imidazo[2,1-i]purine-7-carbaldehyde with bromomalonaldehyde in DMF in the presence of formic acid and 2,6-lutidine, (iii) reductive amination of the formyl group followed by N-alkylation or N-acylation, and (iv) release from the support by acidolytic cleavage of the N-glycosidic bond. Steps (ii) and (iii) have been optimized in some detail by using (adenin-9-yl)acetic acid anchored to a Phe-Wang resin as a model compound.
ABSTRACT A method for synthesis of libraries of 5,1',5'-trisubstituted 2,4&#3... more ABSTRACT A method for synthesis of libraries of 5,1',5'-trisubstituted 2,4'-biimidazoles on a solid support was developed. A trivalent scaffold, 2-(5'-amino-5-formyl-1H,1'H-2,4'-biimidazol-1'-yl)-acetic acid, is first prepd. by a two step synthesis in soln. The product is then coupled to an amino acid loaded Wang resin, further derivatized in two steps and released from the resin. [on SciFinder(R)]
Journal of Organic Chemistry, Nov 6, 2009
A method for the synthesis of libraries of 4(5),1&amp... more A method for the synthesis of libraries of 4(5),1',5'-trisubstituted 2,4'-biimidazoles on a solid support was developed. (1) A trivalent scaffold, 2-(5'-amino-4(5)-formyl-1H,1'H-2,4'-biimidazol-1'-yl)acetic acid, was first prepared in solution by a two-step synthesis from ethyl adenin-9-ylacetate and bromomalonaldehyde. The product was coupled to an amino acid loaded Wang resin and the formyl group was subsequently derivatized either by reductive amination, oximation, or hydrazone formation. The 5'-amino group of the resin-bound biimidazole was then acylated and the products were finally released from the resin and purified. 5'-Amino-2,4'-biimidazole offers a scaffold for lead compounds of drug discovery, possibly useful in finding leads for protein kinase inhibitors.
ChemPlusChem, 2011
A method for the synthesis of 7-substituted 3-β-D-ribofuranosyl-3H-imidazo[2,1-i]purines has been... more A method for the synthesis of 7-substituted 3-β-D-ribofuranosyl-3H-imidazo[2,1-i]purines has been devised whereby compounds were prepared in a few steps from a common intermediate, 3-(2′,3′-O-isopropylidene-β-D-ribofuranosyl)-3H-imidazo[2,1-i]purine-7-carbaldehyde, obtained from the reaction of 2′,3′-O-isopropylideneadenosine with bromomalonaldehyde. The formyl group of the carbaldehyde was subsequently reductively aminated and the resulting secondary amines were then further derivatized either by acylation, lactamization or reductive alkylation.
ABSTRACT A method for synthesis of libraries of 5,1',5'-trisubstituted 2,4&#3... more ABSTRACT A method for synthesis of libraries of 5,1',5'-trisubstituted 2,4'-biimidazoles on a solid support was developed. A trivalent scaffold, 2-(5'-amino-5-formyl-1H,1'H-2,4'-biimidazol-1'-yl)-acetic acid, is first prepd. by a two step synthesis in soln. The product is then coupled to an amino acid loaded Wang resin, further derivatized in two steps and released from the resin. [on SciFinder(R)]
The originality of this thesis has been checked in accordance with the University of Turku qualit... more The originality of this thesis has been checked in accordance with the University of Turku quality assurance system using the Turnitin OriginalityCheck service. Cover illustration: A stereomicroscope image of dry aminomethyl copoly(styrene-1% divinylbenzene) particles used in solid-phase synthesis. (by Tuomas Karskela)
Collection Symposium Series, 2008
ABSTRACT A method for synthesis of libraries of 5,1',5'-trisubstituted 2,4&#3... more ABSTRACT A method for synthesis of libraries of 5,1',5'-trisubstituted 2,4'-biimidazoles on a solid support was developed. A trivalent scaffold, 2-(5'-amino-5-formyl-1H,1'H-2,4'-biimidazol-1'-yl)-acetic acid, is first prepd. by a two step synthesis in soln. The product is then coupled to an amino acid loaded Wang resin, further derivatized in two steps and released from the resin. [on SciFinder(R)]
ChemInform, 2011
ABSTRACT Substituted purine derivatives are synthesized via reductive amination of isopropylidene... more ABSTRACT Substituted purine derivatives are synthesized via reductive amination of isopropylidene-protected carbaldehyde (III).
Collection of Czechoslovak Chemical Communications, 2011
ABSTRACT A method for the synthesis of 7-substituted 3-β-D-ribofuranosyl-3H-imidazo[2,1-i]purines... more ABSTRACT A method for the synthesis of 7-substituted 3-β-D-ribofuranosyl-3H-imidazo[2,1-i]purines was devised, whereby the compds. were prepd. in a few steps from a common intermediate, 3-(2',3'-O-isopropylidene-β-D-ribofuranosyl)-3H-imidazo[2,1-i]purine-7-carbaldehyde, obtained from the reaction of 2',3'-O-isopropylideneadenosine with BrCH(CHO)2. The CHO group of the carbaldehyde was subsequently reductively aminated, and the resulting secondary amines were then further derivatized either by acylation, lactamization, or reductive alkylation.
The Journal of organic chemistry, Jan 15, 2002
Synthetic glycoclusters are extensively used as mimetics of naturally occurring, multivalent carb... more Synthetic glycoclusters are extensively used as mimetics of naturally occurring, multivalent carbohydrate ligands in various glycobiological applications. Their preparation, however, is far from trivial, and it still is a limiting factor in the study of carbohydrate binding. We herein report the synthesis of an orthogonally protected building block, N-Alloc-N'-Boc-N' '-Fmoc-alpha,alpha-bis(aminomethyl)-beta-alanine (1), and its use in the preparation of triantennary peptide glycoclusters (21-24) on a solid support. The assembly of the clusters involves removal of the amino protections of the solid-supported branching unit 1 in the order Fmoc, Boc, and Alloc, and subsequent coupling of peracetylated O-(glycopyranosyl)-N-Fmoc-L-serine pentafluorophenyl esters (galactose, glucose, mannose, and ribose) to each amino group exposed.
Journal of Agricultural and Food Chemistry, Aug 1, 2002
Sulfa antibiotics (sulfonamides) are derivatives of p-aminobenzenesulfonamide that are widely use... more Sulfa antibiotics (sulfonamides) are derivatives of p-aminobenzenesulfonamide that are widely used in veterinary medicine. Foods derived from treated animals may be contaminated with these drugs. However, current immunobased sulfonamide detection methods are unfit for screening of products because they are either too insensitive or specific for a few compounds only. An immunoassay capable of detecting all sulfas in a single reaction would be ideal for screening. For development of a binder capable of binding all sulfas, a protein engineering approach was chosen and the properties of monoclonal antibody 27G3 were improved with mutagenesis followed by selection with phage display. Several different mutant antibodies were isolated. The cross-reaction profile of the best mutant antibody was significantly improved over that of the wild-type antibody: it was capable of binding 9 of the tested 13 sulfonamides within a narrow concentration range and also bound the rest of the sulfas, albeit within a wider concentration range.
European Journal of Organic Chemistry, 2001
Orthogonally protected bis (aminomethyl) malonic acid (1) was synthesized and used as a key build... more Orthogonally protected bis (aminomethyl) malonic acid (1) was synthesized and used as a key building block for the construction of cyclic peptide conjugates on a solid support. The applicability of the building block was demonstrated by preparation of 19 backbone ...
Journal of Biological Chemistry, 2001
Phenoxybenzamine (PB), a classical alpha-adrenergic antagonist, binds irreversibly to the alpha-a... more Phenoxybenzamine (PB), a classical alpha-adrenergic antagonist, binds irreversibly to the alpha-adrenergic receptors (ARs). Amino acid sequence alignments and the predicted helical arrangement of the seven transmembrane (TM) domains suggested an accessible cysteine residue in transmembrane 3 of the alpha(2)-ARs, in position C(3.36) (in subtypes A, B, and C corresponding to amino acid residue numbers 117/96/135, respectively), as a possible site for the PB interaction. Irreversible binding of PB to recombinant human alpha(2)-ARs (90 nm, 30 min) reduced the ligand binding capacity of alpha(2A)-, alpha(2B)-, and alpha(2C)-AR by 81, 96, and 77%. When the TM3 cysteine, Cys(117), of alpha(2A)-AR was mutated to valine (alpha(2A)-C117V), the receptor became resistant to PB (inactivation, 10%). The beta(2)-AR contains a valine in this position (V(3.36); position number 117) and a cysteine in the preceding position (Cys(116)) and was not inactivated by PB (10 microm, 30 min) (inactivation 26%). The helical orientation of TM3 was tested by exchanging the amino acids at positions 116 and 117 of the alpha(2A)-AR and beta(2)-AR. The alpha(2A)-F116C/C117V mutant was resistant to PB (inactivation, 7%), whereas beta(2)-V117C was irreversibly inactivated (inactivation, 93%), confirming that position 3.36 is exposed to receptor ligands, and position 3.35 is not exposed in the binding pocket.
ABSTRACT Substituted purine derivatives are synthesized via reductive amination of isopropylidene... more ABSTRACT Substituted purine derivatives are synthesized via reductive amination of isopropylidene-protected carbaldehyde (III).
Collection of Czechoslovak Chemical Communications
A method for the synthesis of 7-substituted 3-β-D-ribofuranosyl-3H-imidazo[2,1-i]purines was devi... more A method for the synthesis of 7-substituted 3-β-D-ribofuranosyl-3H-imidazo[2,1-i]purines was devised, whereby the compds. were prepd. in a few steps from a common intermediate, 3-(2',3'-O-isopropylidene-β-D-ribofuranosyl)-3H-imidazo[2,1-i]purine-7-carbaldehyde, obtained from the reaction of 2',3'-O-isopropylideneadenosine with BrCH(CHO)2. The CHO group of the carbaldehyde was subsequently reductively aminated, and the resulting secondary amines were then further derivatized either by acylation, lactamization, or reductive alkylation.
Journal of Agricultural and Food Chemistry, 2002
Sulfa antibiotics (sulfonamides) are derivatives of p-aminobenzenesulfonamide that are widely use... more Sulfa antibiotics (sulfonamides) are derivatives of p-aminobenzenesulfonamide that are widely used in veterinary medicine. Foods derived from treated animals may be contaminated with these drugs. However, current immunobased sulfonamide detection methods are unfit for screening of products because they are either too insensitive or specific for a few compounds only. An immunoassay capable of detecting all sulfas in a single reaction would be ideal for screening. For development of a binder capable of binding all sulfas, a protein engineering approach was chosen and the properties of monoclonal antibody 27G3 were improved with mutagenesis followed by selection with phage display. Several different mutant antibodies were isolated. The cross-reaction profile of the best mutant antibody was significantly improved over that of the wild-type antibody: it was capable of binding 9 of the tested 13 sulfonamides within a narrow concentration range and also bound the rest of the sulfas, albeit within a wider concentration range.
Organic & Biomolecular Chemistry, 2006
A method for solid-supported synthesis of N,N-disubstituted (3H-imidazo[2,1-i]purin-7-yl)methyl a... more A method for solid-supported synthesis of N,N-disubstituted (3H-imidazo[2,1-i]purin-7-yl)methyl amines has been developed. The key features of this library synthesis are: (i) immobilization of commercially available N6-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-deoxyadenosine 3'-(2-cyanoethyl N,N-diisopropylphosphoramidite) by phosphitylation to a hydroxyl-functionalized support, (ii) quantitative conversion of the deprotected adenine base to 3H-imidazo[2,1-i]purine-7-carbaldehyde with bromomalonaldehyde in DMF in the presence of formic acid and 2,6-lutidine, (iii) reductive amination of the formyl group followed by N-alkylation or N-acylation, and (iv) release from the support by acidolytic cleavage of the N-glycosidic bond. Steps (ii) and (iii) have been optimized in some detail by using (adenin-9-yl)acetic acid anchored to a Phe-Wang resin as a model compound.
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Papers by Tuomas Karskela