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Int J Pept Res Ther (2009) 15:211218 DOI 10.1007/s10989-009-9177-0
To Rink or Not to Rink Amide Link, that is the Question to Address for More Economical and Environmentally Sound Solid-Phase Peptide Synthesis
Tarek Kassem David Sabatino Xin Jia X. X. Zhu William D. Lubell
Accepted: 17 March 2009 / Published online: 15 April 2009 Springer Science+Business Media, LLC 2009
Abstract A comparative study is presented on the solid-phase peptide synthesis (SPPS) of the acyl carrier protein (ACP 6574) sequence on a series of Rink amide resins possessing different matrix structures: poly(vinyl alcohol)-graft-poly(ethylene glycol) (PVA-g-PEG, 4), Tentagel-SRAM (TG, 5), NovaGel (NG, 6), ChemMatrix (CM, 7) and polystyrene-divinylbenzene (PS-DVB, 8). In this comparison, the PEG-containing resins proved signicantly better suited for the synthesis of pure ACP target sequence than the conventional PS-DVB solid supports (7590% versus 52% crude purity). Amongst themselves, the PEG resins 4-7 exhibited similar capacity for providing pure peptide. Selecting PVA-g-PEG resin for a comparison of Rink amide linker versus no linker, the ACP (6574) sequence was synthesized directly on the PVA-g-PEG resin 1, under identical conditions as employed in the synthesis on resin 4 bearing the Fmoc Rink linker, except for the nal cleavage step, which was performed under more environmentally sound conditions using ester displacement with aqueous ammonia. Relative to its Rink amide counterpart 4, PVA-g-PEG resin 1 was cheaper to produce and possessed twice as much loading capacity (0.48 vs. 0.81 mmol/g). Moreover, Rink-less resin 1 gave higher yields of isolated pure peptide (61 vs. 45%) relative to its Fmoc Rink linker counterpart 4. In light of these results, the importance of the linker has been brought into question. As the need for large
scale solid-phase peptide synthesis grows with greater demand for peptide products, ideal resins should be inexpensive to produce and employable under environmentally sound conditions to provide pure products. In this light, PVA-g-PEG resin 1 has demonstrated signicant promise for economic and green SPPS.
Keywords Poly(vinyl alcohol)-graft-poly(ethylene glycol) Tentagel-S-RAM Rink-H ChemMatrix resin
Rink amide NovaGel resin Rink amide
polystyrene-divinylbenzene resin Solid support
Peptide synthesis Acyl carrier protein
Introduction
Industrial investment in combinatorial technology and increased market demand for peptide products have fueled a renaissance of interest in solid-phase chemistry for the preparation of peptides, proteins and small...