TentaGel S-OH

Cross-linked polystyrene-ethyleneglycol acrylate resin (CLPSER) was developed for the solid-phase synthesis of peptide by introducing a cross-linker, O,O'-bis(2-acrylamidopropyl)polyethylene glycol(1900) (Acr(2)PEG), into polystyrene. The cross-linker was prepared by treating acryloyl chloride with O,O'-bis(2-aminopropyl) polyethylene glycol(1900) [(NH(2))(2)PEG] in the presence of diisopropylethylamine. The copolymer was prepared either by bulk or inverse suspension copolymerization of Acr(2)PEG(1900) and styrene using sorbitan monolaurate as the suspension stabilizer, and a mixture of ammonium peroxodisulfate and benzoyl peroxide as the radical initiators. The resin was characterized using gel-phase (13)C NMR, infrared (KBr) spectroscopic techniques and the morphological features of the resin were investigated using scanning electron microscopy photographs. CLPSER showed excellent swelling in a broad range of solvents and was found to be chemically inert to various reagents and solvents used in solid-phase peptide synthesis. To demonstrate the usefulness of the new resin in polypeptide synthesis, the support was derivatized with an 'internal reference' amino acid (norleucine) and a handle 4-(4-hydroxymethyl-3-methoxy)butyric acid. The new resin was compared with commercial supports such as Merrifield and Sheppard resins by synthesizing an acyl carrier protein (65-74) fragment under the same experimental conditions. HPLC profiles revealed the high efficiency of the newly developed support. Resin capability in peptide synthesis was further demonstrated by the solid phase synthesis of a 25-residue peptide from the E2/NS1 region hepatitis C viral polyprotein.

Spherical crosslinked poly(vinyl alcohol) (PVA) beads with good mechanical stability were prepared by reverse-suspension polymerization, using dimethyl sulfoxide (DMSO) as a cosolvent in an aqueous phase. Poly(ethylene glycol)s with varying chain lengths were grafted onto the PVA beads by anionic polymerization of ethylene oxide. The thermal behavior, morphology, and swelling were evaluated for each of the new polymer matrices. High loading and good swelling in water and organic solvents were characteristic of the PEG-grafted PVA beads. The polymer beads also exhibited good mechanical and chemical stability and were unaffected by treatment with 6 N HCl and with 6 N NaOH. The hydroxyl groups of the PVA-PEG beads were converted into aldehyde, carboxylic acid, and isocyanate functions to provide scavenger resins and were extended by way of a benzyl alcohol in a Wang linker. The transglutaminase substrates dipeptides (Z-Gln-Gly) and heptapeptides (Pro-Asn-Pro-Gln-Leu-Pro-Phe) were synthesized on PVA-PEG_5, PVA-PEG_20, and the Wang linker-derivatized PVA-PEG resins. The cleavage of the peptides from the resins using MeOH/NH3 mixture at different temperatures (0 degrees C and room temp) and 50% TFA/DCM provided, respectively, peptide methyl esters, amides, and acids in good yields and purity as assessed by LC-MS analysis.

In a preliminary investigation by our group, we found that poly(styrene-oxyethylene) graft copolymers (PS-PEG), for example, TentaGel resins, are advantageous for gel-phase (13)C NMR spectroscopy. Because of the solution-like environment provided by the PS-PEG resins, good spectral quality of the attached moiety can be achieved, which is useful for nondestructive on-resin analysis. The general drawbacks of such resins are low loading capacities and the intense signal in the spectra resulting from the PEG linker (>50 units). Here, we describe the characterization of solvent-dependent swelling and reaction kinetics on a new type of resin for solid-phase organic synthesis (SPOS) that allows an accurate monitoring by gel-phase NMR without the above disadvantages. A series of polystyrene-oligo(oxyethylene) graft copolymers containing monodisperse PEG units (n = 2-12) was synthesized. A strong correlation between the linker (PEG) length and the line widths in the (13)C gel-phase spectra was observed, with a grafted PEG chain of 8 units giving similar results in terms of reactivity and gel-phase NMR monitoring to TentaGel resin. Multistep on-resin reaction sequences were performed to prove the applicability of the resins in solid-phase organic synthesis.