Monitoring the Chemical Assembly of a Transmembrane Bradykinin Receptor Fragment: Correlation Between Resin Solvation, Peptide Chain Mobility, and Rate of Coupling

• Published in: European journal of organic chemistry Vol. 2002; no. 21; pp. 3686 - 3694
• Main Authors: Oliveira, Eliandre, Cilli, Eduardo M., Miranda, Antonio, Jubilut, Guita N., Albericio, Fernando, Andreu, David, Paiva, Antonio C. M., Schreier, Shirley, Tominaga, Mineko, Nakaie, Clovis R.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.11.2002; WILEY‐VCH Verlag
• Subjects: Bradykinin; EPR spectroscopy; Membranes; Peptides; Resins
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/1099-0690(200211)2002:21<3686::AID-EJOC3686>3.0.CO;2-5

A combined resin solvation‐peptide chain motion and kinetics of coupling reaction approach was applied to monitor details of the synthesis of TM‐34, a 34‐residue transmembrane segment of the bradykinin receptor. The dynamics of resin‐bound peptide fragments attached to a stable free radical amino acid were examined by EPR spectroscopy. In agreement with an abrupt decrease (from 83 to 43%) in peptide purity occurring in the 12−16 region when DMF was used, a much more strongly immobilized chain population was detected, especially at the 12‐mer stage. Conversely, faster couplings and improved synthesis were observed in 20% DMSO/NMP, probably due to the higher chain mobility in this mixed solvent. In addition, findings relating to solvation of peptide resins seemed to corroborate the previously advanced proposition that the 1:1 sum of electron acceptor and electron donor properties of a solvent can be considered to be an alternative and more appropriate parameter for its polarity. (© Wiley‐VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)