Lm. Varanda et Mtm. Miranda, SOLID-PHASE PEPTIDE-SYNTHESIS AT ELEVATED-TEMPERATURES - A SEARCH FORAN OPTIMIZED SYNTHESIS CONDITION OF UNSULFATED CHOLECYSTOKININ-12, The journal of peptide research, 50(2), 1997, pp. 102-108
A systematic investigation of solid-phase peptide synthesis at elevate
d temperatures using the well-known aggregating peptide acyl carrier p
rotein (65-74) and the unsulfated cholecystokinin-8 as models is prese
nted. The main goal of the investigation was the determination of an o
ptimized experimental condition for the synthesis of unsulfated cholec
ystokinin-12. Of the elevated temperatures used, 60 degrees C was the
most appropriate. The efficiency of ,N'-diisopropylcarbodiimide/1-hydr
oxybenzotriazole (DIG/HOBt) in 25% dimethyl sulfoxide (DMSO)/toluene a
t this temperature was similar to that of 1-H-benzotriazole-1-yl)-1.1.
3.3-tetramethyluronium tetrafluoroborate (TBTU). Interestingly, this c
oupling reagent was more efficient than TB?ZI, benzotriazol-1-yl oxytr
is(dimethylamino)phosphonium and 7-azabenzotriazol-1-yl)-1,1,3,3-tetra
methyluronium hexafluorophosphate in N-methylpyrrolidone. 25%DMSO/tolu
ene proved to be suitable for the swelling of the resins phenylacetami
domethyl, methylbenzhydrylamine, hydroxymethylphenoxy, 4-(benzyloxy)-2
',4'-dimethoxybenzhydrylamine, 4-(2',3'dimethoxyphenyl-Fmoc-aminomethy
l) ??phenoxy and succinylamido-2',2',4'-trimethoxy)benzhydrylamine. Th
ose 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 e
ncountered. These data confirm the usefulness of solid-phase peptide s
ynthesis at elevated temperatures and extend its applicability. (C) Mu
nksgaard 1997.