Effectiveness of the suzuki-miyaura cross-coupling reaction for solid-phase peptide modification.
The Suzuki-Miyaura (SM) cross-coupling reaction has recently become one of the most efficient methods for C-C bond construction opening a wide range of opportunities in organic synthesis. This study focused on the evaluation of the use of the SM reaction to modify peptides using a solid-phase synthesis approach, an avenue that was still not investigated intensively. We used as a peptide model [Ala (1,2,3), Leu (8)]Enk linked to a polystyrene support on which it was previously assembled. The aromatic residues Tyr (4) and Phe (7) of [Ala (1,2,3), Leu (8)]Enk were respectively substituted with p-iodo-Phe, and an SM-related strategy was developed. Results indicated that the reaction conditions involving K 3PO 4 or Na 2CO 3 (base), DMF (solvent), Pd(PPh 3) 4 (catalyst), and temperatures ranging from 50 to 80 degrees C during 20 h were found as optimal. Finally applying those optimal conditions, a series of [Ala (1,2,3), Leu (8)]Enk analogs modified at Tyr (4) or Phe (7) positions was synthesized using diverse boronic acid derivatives.
Doan
Ngoc-Duc
ND
Laboratoire d'études moléculaires et phamacologiques des peptides (LEMPP), INRS-Institut Armand-Frappier, Université du Québec, 245 Boul. Hymus, Pointe-Claire, QC, Canada.
Bourgault
Steve
S
Létourneau
Myriam
M
Fournier
Alain
A
D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D020650:Combinatorial Chemistry Techniques / Q000379:methods; D003432:Cross-Linking Reagents / Q000737:chemistry; D010165:Palladium; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D011137:Polystyrenes / Q000737:chemistry; D011487:Protein Conformation; D012997:Solvents / Q000737:chemistry; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013696:Temperature
D003432:Cross-Linking Reagents; D010455:Peptides; D011137:Polystyrenes; D012997:Solvents; D010165:Palladium