PEG-PS support

PEG-PS supports were developed to allow better solvation of the growing peptide chain in polar aprotic solvents commonly used for peptide synthesis. The PEG resins were also shown to have excellent mechanical stability, which allows their use in continuous-flow systems [19]. Other PEG-con-taining supports include poly(trimethylolpropane ethoxy late [14/3 EO/ OH)triacrylate-co-allylamine] (CLEAR) [28] and poly(A,A-dimethylac-rylamide-co-bisacrylamido polyethylene glycol-co-monoacrylamidopoly-ethylene glycol) (PEGA) [29,30], and have demonstrated promising properties. 

A wash-gas-wash-gas procedure was placed at the end of each stage of the synthesis cycle. This operation more effectively cleaned the PEG-PS support of residual reagents and resulted in improved synthesis performance. DMF is used as the wash solvent for each stage. The PNA protocol also incorporates an optional wash at the end of a synthesis. This wash uses either dichloromethane (DCM) or methanol to rinse the resin so that it may be rapidly dried and more easily removed from the column housing, A DCM resin wash is recommended for long-term storage of PNA on a solid support. Other than this optional wash, no chlorinated solvents are used in Fmoc PNA synthesis. 

Two PEG-PS supported BINAP ligands have been prepared by reaction of a suitably derivitized support and dihydroxy BINAP 112 (Scheme 53). Starting from acid-functionalized support 111, 112 was attached to form 113. A ligand loading of 0.1 mmol g was obtained. Starting from bromo-functionalized support 114, supported BINAP 115 was made by first treating 112 with BuLi before adding the resin. 

An alternative approach to a PS-PEG amphiphilic BINAP has been reported involving reaction of BINAP-carboxylic acid 116 with an amine-functionalized PEG-PS support to give 117 (Scheme 54). ... 

The PEG-PS supported BINAPs 113 and 115 were used as ligands for Rh-catalyzed asymmetric isomerizations, the metal complexes being formed in situ by reaction of the supported ligands with [Rh(cod)2] [CF3S03]. Both these and their silica-immobilized counterparts were found to be less reactive than their homogenous analogs... 

Portions of this work are described in the Ph.D. Thesis of S. Zalipsky, University of Minnesota, 1987 results from this dissertation and numerous additional findings concerning the use of PEG-PS supports for peptide synthesis were presented in preliminary form at several meetings [1-5]. Further documentation and additional examples of the preparation, ion-ex-... 

The present report details our initial experiences with a novel class of supports for peptide synthesis, polyethylene glycol-polystyrene (PEG-PS) graft resins (Fig. 1). Our PEG-PS supports contain approximately equal weight amounts of the two polymer... 

Fig. 5. Analytical HPLC of crude samples directly after cleavage from several solid-phase syntheses of ACP (65-74) amide. HPLC was performed on a Vydac reversed-phase column (250 x 4.6 mm I.D.) with a linear gradient over 15 min using 0.01 M aqueous HCl and CH3CN from 9 1 to 1 1, flow-rate 1.2 ml/min UV absorbance 215 nm. See Sections 2.8 and 2.10 for synthetic details. (A) Synthesis carried out on PAL-PS resin with CHjClj-DMF as solvent. (B) Synthesis carried out on PAL-PEG-PS support in parallel with synthesis shown in panel A. (C) Synthesis carried out on PAL-PEG-PS support, using acetonitrile as the solvent for all coupling steps and washes.

This work has reported on a chemically well defined class of graft polymer resin supports combining the mechanical stability of a hydrophobic cross-linked PS matrix with the beneficial features of readily solvatable polar PEG chains. These PEG-PS supports show excellent physicochemical properties and are demonstrably useful for solid-phase peptide synthesis. The PEG/PS ratio can be controlled readily on the basis of the level of PS functionalization and/or the molecular weight of heterobifunctional PEG used. The PEG-PS supports prepared as described... 

PEG-PS supports have a defined and reproducible structure that comprises approximately 60 wt% of polyethylene glycol providing a support that is physically robust (38). PEG-PS resins swell appreciably in a range of solvents and are superior to polystyrene supports for the construction of more complex peptides, including those containing cyclic (lactam and disulphides), branched, and post-translational modified moieties. 

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