| 1. |
- Adlercreutz, Patrick, et al.
(författare)
-
Synthetic polymers as solubilizing vehicles for enzymes in water-poor media
- 1994
-
Ingår i: Bioorganic and Medicinal Chemistry. - : Elsevier BV. - 0968-0896. ; 2:6, s. 529-533
-
Forskningsöversikt (refereegranskat)abstract
- A recent method for exposing enzymes to organic solvents is reviewed. By complex formation between the enzyme and polymers that per se are soluble in organic solvents it is possible to disperse the enzyme in the organic medium in such a way that an optically transparent (in the visible region) solution is obtained. After reaction, the separation of the enzyme from the organic medium can be obtained simply by addition of water. The enzyme can be recovered from the water phase. Physicochemical studies have revealed that the enzyme is more stable in the complex-bound form.
|
|
| 2. |
- Björup, Peter, et al.
(författare)
-
Reaction medium engineering in enzymatic peptide fragment condensation : Synthesis of eledoisin and LH-RH
- 1998
-
Ingår i: Bioorganic and Medicinal Chemistry. - 0968-0896. ; 6:7, s. 891-901
-
Tidskriftsartikel (refereegranskat)abstract
- The influence of different reaction systems on α-chymotrypsin-catalyzed synthesis of eledoisin and LH-RH peptides from (7+4) and (5+5) fragments was investigated. The peptide yield was determined in the following systems: buffered aqueous media, frozen solutions, organic media, and cosolvent mixtures. The experimental set up was tailored to allow the screening of an array of conditions with minimum consumption of peptide fragments (2.1 and 2.5mM). The best yields (22% yield for eledoisin and 68% yield for LH-RH) were obtained in buffered aqueous solutions. It was found that the choice of buffer had a strong influence on the peptide yield; boric-borate and ammonium acetate buffers at pH 9, gave the best results. In buffered aqueous systems, both syntheses were scaled up by using a 10-fold increase in fragment concentration (21 and 25mM). Under these conditions the yields rose to 57% and 80% of eledoisin and LH-RH, respectively. Moreover, during the synthesis of eledoisin and in the presence of boric-borate buffer pH 9, the peptide precipitated from the reaction medium preventing a secondary hydrolysis and facilitating the in situ product purification. Copyright (C) 1998 Elsevier Science Ltd.
|
|
| 3. |
- Clapés, Pere, et al.
(författare)
-
Enzymatic peptide synthesis in low water content systems : Preparative enzymatic synthesis of [Leu]- and [Met]-enkephalin derivatives
- 1995
-
Ingår i: Bioorganic and Medicinal Chemistry. - 0968-0896. ; 3:3, s. 245-255
-
Tidskriftsartikel (refereegranskat)abstract
- A novel total enzymatic synthesis of [Leu]- and [Met]-enkephalin derivatives was accomplished in low-water content systems at a preparative scale. α-Chymotrypsin, papain, thermolysin and bromelain adsorbed on Celite were used as catalysts. Organic solvents such as acetonitrile and ethyl acetate with small amounts of buffer added or at specific water activity were used as reaction media. Simple readily available amino acid ester derivatives were used as starting building blocks. This feature allowed the possibility of using the products in one step directly as acyl-donor ester, without any chemical or enzymatic modification, in the next enzymatic coupling. The optimal strategy for the synthesis of the enkephalin derivatives was different depending on the carboxy terminal group. The preparation of the carboxy-terminal amide derivatives (R-Tyr-Gly-Gly-Phe-Leu[Met]-NH2) was achieved via 4 + 1 fragment condensation catalyzed by α-chymotrypsin. The carboxy-terminal ethyl ester derivatives (R-Tyr-Gly-Gly-Phe-Leu[Met]-OEt) were obtained via 2 + 3 condensation catalyzed by bromelain, a quite unusual protease for peptide synthesis but more effective than papain in this coupling. Both syntheses were carried out in four enzymatic steps and one or two chemical deprotection steps routinely used in peptide synthesis. The overall yields of pentapeptide derivatives were between 40-54% of pure product.
|
|
| 4. |
- Ellervik, Ulf, et al.
(författare)
-
Calculated conformations of sialyl-Lex- and sialyl-Lea-lactones
- 1994
-
Ingår i: Bioorganic and Medicinal Chemistry. - 0968-0896. ; 2:11, s. 1261-1266
-
Tidskriftsartikel (refereegranskat)abstract
- The minimum energy conformations of the four sterically reasonable SLex and SLea lactones were calculated using the molecular mechanics force-field MM2(91). The tetrasaccharide lactone involving the 3- and 2-position of the Gal moiety was found to be more stable than the 3,4-lactone both for SLex and SLea. © 1994.
|
|
| 5. |
- Holm, B, et al.
(författare)
-
Role of the galactosyl moiety of collagen glycopeptides for T-cell stimulation in a model for rheumatoid arthritis
- 2003
-
Ingår i: Bioorganic & Medicinal Chemistry. - 0968-0896. ; 11:18, s. 3981-3987
-
Tidskriftsartikel (refereegranskat)abstract
- Two protected derivatives of beta-D-galactopyranosyl-5-hydroxy-L-lysine, in which HO-4 of galactose has been O-methylated or replaced by fluorine, have been prepared. The building blocks were incorporated at position 264 of the peptide fragment CII259-273 from type II collagen by solid-phase synthesis. The ability of these two glycopeptides, and two CII259-273 glycopeptides in which HO-4 of galactose was either unmodified or deoxygenated, to elicit responses from T-cell hybridomas obtained in a mouse model for rheumatoid arthritis was then determined. The hybridomas were all highly sensitive towards modifications at C-4 of the beta-D-galactosyl residue of CII259-273, highlighting the role of HO-4 as an important contact point for the T-cell receptor. Most likely, this glycopeptide hydroxyl group is involved in hydrogen bonding with the T-cell receptor. (C) 2003 Elsevier Ltd. All rights reserved.
|
|
| 6. |
- Larsson, Andreas, et al.
(författare)
-
Quantitative studies of the binding of the class II PapG adhesin from uropathogenic Escherichia coli to oligosaccharides.
- 2003
-
Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier. - 0968-0896 .- 1464-3391. ; 11:10, s. 2255-2261
-
Tidskriftsartikel (refereegranskat)abstract
- Binding of the class II PapG adhesin, found at the tip of filamentous pili on Escherichia coli, to the carbohydrate moiety of globoseries glycolipids in the human kidney is a key step in development of pyelonephritis, a severe form of urinary tract infection. An assay based on surface plasmon resonance for quantification of the binding of the class II PapG adhesin to oligosaccharides has been developed. Using this assay dissociation constants ranging from 80 to 540 M were determined for binding of the PapG adhesin to di-pentasaccharide fragments from the globoseries of glycolipids. A series of galabiose derivatives, modified at the anomeric position, O-2′ or O-3′, was also investigated. The anomeric position appeared to be the most promising for development of improved inhibitors of PapG-mediated adhesion of E. coli. p-Methoxyphenyl galabioside was found to be most potent (Kd=140 M), and binds to PapG almost as well as the Forssman pentasaccharide.
|
|
| 7. |
- Nilsson, Ulf, et al.
(författare)
-
PapG adhesin from E. coli J96 recognizes the same saccharide epitope when present on whole bacteria and as isolated protein
- 1996
-
Ingår i: Bioorganic and Medicinal Chemistry. - 0968-0896. ; 4:11, s. 1809-1817
-
Tidskriftsartikel (refereegranskat)abstract
- Purified PapG adhesin from the genetically well-defined uropathogenic Escherichia coli strain J96, as well as whole bacteria, were bound to microtiter plates that carried covalently bound globotetraose and galabiose. The binding was inhibited by soluble saccharide derivatives corresponding to the globoseries of glycolipids, including all di-, tri-, tetra-, and pentasaccharide fragments of the Forssman antigen and all monodeoxy analogues of galabiose. Analysis of the inhibition pattern showed no significant difference between purified adhesin and whole bacteria. The glucose unit at the reducing end of the natural saccharides was detrimental to PapG binding since deletion of the glucose unit increased the inhibitory power 10-20 fold. The five hydroxyl groups HO-6, -2', -3', -4', -6' of the galabiose unit were shown to be important for PapG binding, presumably via intermolecular hydrogen bonds.
|
|
| 8. |
- Persson, Tina, et al.
(författare)
-
Synthesis of 2'-Deoxyuridine 5'-(α,β-Imido)triphosphate: A Substrate Analogue and Potent Inhibitor of dUTPase
- 1996
-
Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896. ; 4:4, s. 553-556
-
Tidskriftsartikel (refereegranskat)abstract
- The dUDP analogue, 2'-deoxyuridine 5'-(α,β-imido)diphosphate (dUPNP) was synthesized. The corresponding triphosphate analogue (dUPNPP) was prepared by enzymic phosphorylation of dUPNP using the enzyme pyruvate kinase and phosphoenolpyruvate as the phosphate donor. This method was successful in phosphorylating the imidodiphosphate analogue of 2'-deoxythymidine (dTPNP) to 2'-deoxythymidine 5'-(α,β-imido)triphosphate (dTPNPP), in contradiction to a previous report. The properties of dUPNPP have been tested using the enzyme dUTPase from Escherichia coli. This enzyme, having a crucial role in nucleotide metabolism, is strictly specific for its substrate (dUTP) and catalyzes the hydrolysis of the α,β-bridge, resulting in dUMP and pyrophosphate. Replacement of the α,β-bridging oxygen in dUTP with an imido group resulted in a nonhydrolyzable substrate analogue and a potent competitive inhibitor of dUTPase (Ki=5μM). The analogue prepared (dUPNPP) may be utilized in crystallographic studies of the active site of dUTPase to provide knowledge about specific interactions involved in substrate binding and as a parental compound in design of dUTPase inhibition for medical purposes.
|
|
| 9. |
- Tuite, Eimer, 1966, et al.
(författare)
-
Intercalative interactions of ethidium dyes with triplex structures
- 1995
-
Ingår i: Bioorganic and Medicinal Chemistry. - 0968-0896 .- 1464-3391. ; 3:6, s. 701-711
-
Tidskriftsartikel (refereegranskat)abstract
- The binding of phenanthridine dyes to tripler poly(dT)*poly(dA). poly(dT) and its precursor duplex poly(dA). poly(dT) is characterized using linear dichroism and circular dichroism spectroscopy, and thermal denaturation. The two monomeric dyes ethidium bromide and propidium iodide are shown to behave similarly to each other in intercalating into and stabilizing both the duplex and the tripler structures. However, contrary to expectations, the extra cationic side-chain of propidium iodide provides no significant extra stabilization of tripler compared with ethidium bromide, although propidium does stabilize the duplex more than ethidium. The monomeric dyes appear to have somewhat different binding geometries with the duplex and tripler polymers. The dimeric dye ethidium homodimer is found to bis-intercalate in the tripler as well as the duplex but, in contrast to the monomers, no variation in geometry between duplex and tripler is observed. However, although dimer stabilizes the duplex, it has no effect on the thermal stability of the tripler. This lack of binding preferentiality of the dimer for tripler compared with the monomeric dyes indicates greater constraints on the accommodation of a bis-intercalator in the tripler structure than in the duplex.
|
|
| 10. |
- Dahlgren, Anders, et al.
(författare)
-
New inhibitors of the malaria aspartyl proteases plasmepsin I and II
- 2003
-
Ingår i: Bioorganic & Medicinal Chemistry. - 0968-0896 .- 1464-3391. ; 11:16, s. 3423-3437
-
Tidskriftsartikel (refereegranskat)abstract
- New inhibitors of plasmepsin I and II, the aspartic proteases of the malaria parasite Plasmodium falciparum, are described. From paralell solution phase chemistry, several reversed-statine type isostere inhibitors, many of which are aza-peptides, have been prepared. The synthetic strategy delivers the target compounds in good to high overall yields and with excellent stereochemical control throughout the developed route. The final products were tested for their plasmepsin I and II inhibiting properties and were found to exhibit modest but promising activity. The best inhibitor exhibits Ki values of 250 nM and 1.4 µM for Plm I and II, respectively. © 2003 Elsevier Ltd. All rights reserved.
|
|
