Journal of Peptide Science J. Peptide Sci. 5: 577–581 (1999) Solid Phase Synthesis of Hydrophobic Peptides on 1,6-Hexanediol Diacrylate Cross-linked Polystyrene Resin JAYA T. VARKEY a, * and V.N. RAJASEKHARAN PILLAI b a Department of Chemistry, University of Minnesota, Minneapolis, USA b School of Chemical Sciences, Mahatma Gandhi University, Kottayam, Kerala, India 686 686 560 Received 23 July 1999 Accepted 31 July 1999 Abstract: The synthesis of three hydrophobic peptides, which are partial sequences of thioredoxin, on a newly developed, flexible 1,6-hexanediol diacrylate cross-linked polystyrene, in good yield and purity, is described. Copyright © 1999 European Peptide Society and John Wiley & Sons, Ltd. Keywords: flexible support; hydrophobic peptides; PS-HDODA resin; solid phase peptide synthesis INTRODUCTION The synthesis of hydrophobic peptides is a difficult process because of the non-polar side-chains and because of the coiling nature of the peptides [1]. Peptides that have substantial hydrophobic charac- ter also tend to aggregate with increasing concen- tration [2]. Another related factor is the low solubility of these peptides, which may be a limiting factor in some biological test systems [2]. The design and development of polymer supports having optimum hydrophobic – hydrophilic balance for solid phase peptide synthesis is difficult. Innu- merable investigations dealing with the quantitative aspects of polymer supported reactions during the last two decades have shown that the insoluble support has a significant influence on the bound substrates. The success of solid phase synthesis depends on the swelling characteristics of the poly- mer and the solvation of the peptidyl resin in differ- ent solvents [3]. Hence, polymeric systems that swell and solvate to a high degree in solvents used for peptide synthesis have high reactivities. Based on this principle, polystyrene (PS) cross-linked with 1,6-hexanediol diacrylate (HDODA), with a hydro- phobic – hydrophilic balance optimized based on the extent of cross-linking, has been developed for the synthesis of peptides [4]. In the present study, three hydrophobic partial sequences of thioredoxin were synthesized on a 2% cross-linked polymeric system. Thioredoxin is a naturally occurring sulphur re- ducing protein containing 108 amino acid residues [5]. It has a lot of secondary structure (approxi- mately 38%  -helix and 28%  -structure) [6]. It contains sequences of varying hydrophobic – hydrophilic patterns. The following hydrophobic partial sequences of thioredoxin (T) were synthe- sized: (A) Ala-Ile-Leu-Val-Asp-Phe-Trp-Ala (T 22 – 29) (B) Ile-Gly-Arg-Gly-Ile-Pro-Thr-Leu-Le-Leu-Phe (T 71–81) (C) Thr-Leu-Leu-Leu-Phe (T 77 – 81) These peptides were synthesized by following stan- dard solid phase techniques. The synthesized pep- tides were purified using high performance liquid chromatography (HPLC), fast protein liquid chro- matography (FPLC) and subjected to amino acid analysis. EXPERIMENTAL Materials and Methods Styrene, HDODA, side-chain protected amino acids, dicyclohexyl carbodiimide (DCC), trifluoroacetic * Correspondence to: Department of Chemistry, University of Min- nesota, 139 Smith Hall, 207 Pleasant Street, Minneapolis, MN 55455, USA. Copyright © 1999 European Peptide Society and John Wiley & Sons, Ltd. CCC 1075–2617/99/120577-05$17.50