Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012739 (disseminated intravascular coagulation)
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A systematic investigation of solid-phase peptide synthesis at elevated temperatures using the well-known aggregating peptide acyl carrier protein (65-74) and the unsulfated cholecystokinin-8 as models is presented. The main goal of the investigation was the determination of an optimized experimental condition for the synthesis of unsulfated cholecystokinin-12. Of the elevated temperatures used, 60 degrees C was the most appropriate. The efficiency of N,N'-diisopropylcarbodiimide/1-hydroxybenzotriazole (DIC/HOBt) in 25% dimethyl sulfoxide (DMSO)/toluene at this temperature was similar to that of 2-(1-H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU). Interestingly, this coupling reagent was more efficient than TBTU, benzotriazol-1-yl oxy-tris(dimethylamino)phosphonium and O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate in N-methylpyrrolidone. 25% DMSO/toluene proved to be suitable for the swelling of the resins phenylacetamidomethyl, methylbenzhydrylamine, hydroxymethylphenoxy, 4-(benzyloxy)-2',4'-dimethoxybenzhydrylamine, 4-(2',4'-dimethoxyphenyl-Fmoc-aminomethyl)phenoxy and (4-succinylamido-2',2',4'-trimethoxy)benzhydrylamine. Those polymeric supports were fully compatible with the approach. Under the optimized synthesis condition found in these studies (temperature of 60 degrees C, DIC/HOBt as coupling reagent and 25% DMSO/toluene as solvent), no difficulties related to the aggregation phenomenon were encountered. These data confirm the usefulness of solid-phase peptide synthesis at elevated temperatures and extend its applicability.
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PMID:Solid-phase peptide synthesis at elevated temperatures: a search for and optimized synthesis condition of unsulfated cholecystokinin-12. 927 94

Several conditions have been used in the coupling reaction of stepwise SPPS at elevated temperature (SPPS-ET), but we have elected the following as our first choice: 2.5-fold molar excess of 0.04-0.08 M Boc or Fmoc-amino acid derivative, equimolar amount of DIC/HOBt (1:1) or TBTU/DIPEA (1:3), 25% DMSO/toluene, 60 degrees C, conventional heating. In this study, aimed to further examine enantiomerization under such condition and study the applicability of our protocols to microwave-SPPS, peptides containing L-Ser, L-His, L-Cys and/or L-Met were manually synthesized traditionally, at 60 degrees C using conventional heating and at 60 degrees C using microwave heating. Detailed assessment of all crude peptides (in their intact and/or fully hydrolyzed forms) revealed that, except for the microwave-assisted coupling of L-Cys, all other reactions occurred with low levels of amino acid enantiomerization (<2%). Therefore, herein we (i) provide new evidences that our protocols for SPPS at 60 degrees C using conventional heating are suitable for routine use, (ii) demonstrate their appropriateness for microwave-assisted SPPS by Boc and Fmoc chemistries, (iii) disclose advantages and limitations of the three synthetic approaches employed. Thus, this study complements our past research on SPPS-ET and suggests alternative conditions for microwave-assisted SPPS.
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PMID:Microwave-assisted solid-phase peptide synthesis at 60 degrees C: alternative conditions with low enantiomerization. 1982 81