Polymer-supported biopolymer synthesis: 5. Ultra-high load solid (gel) phase peptide synthesis—the stepwise elaboration of quasi-homogeneous peptide gel networks?

Crosslinked poly(N‐[2‐(4‐hydroxphenyl)ethyl]‐acrylamide) has been modified by conversion of each pendant 4‐hydroxyphenyl group to its 2‐(4‐hydroxymethyl‐phenoxy)ethanoyl‐L‐prolyl ester. This provides a spacer group which makes the polymer matrix suitable for solid (gel) phase peptide synthesis with Fmoc amino acids at ultra‐high load (2.2 mmol g−1 of spacer‐modified support). The selectively labile linkages incorporated in the spacer group provide for peptide detachment by either mild acidolysis or hydrazinolysis. The products of hydrazinolysis of intermediate and final peptide‐matrix assemblies are amenable to analysis by high‐pressure liquid chromatography (HPLC).

Advances in ultra‐high load polymer‐supported peptide synthesis with phenolic supports: 1. A selectively‐labile c‐terminal spacer group for use with a base‐mediated n‐terminal deprotection strategy and fmoc amino acids

Butwell¹,

Haws²,

Epton³

1988

Advances in ultra‐high load polymer‐supported peptide synthesis with phenolic supports: 2. Use of ‘hydrazinolysis‐hplc’ to check for racemization on c‐terminal amino acid loading and to determine peptide homogeneity during synthesis with selectively labile c‐terminal anchoring linkages

Baker

Coffey

Epton

et al. 1988

2, 4‐Dinitrophenyl‐L‐phenylalanine has been coupled to L‐, D‐, and DL‐amino acid phenyl esters pendant upon a polymer matrix. The esters had been prepared by di‐isopropylcarbodiimide‐mediated condensation, catalyzed by 4‐dimethylaminopyridine. Reverse phase high pressure liquid chromatography (HPLC), using elution solvents consisting of 10 vol.‐% trifluoroacetic acid in water/acetonitrile mixtures, has been used to investigate the 2,4‐dinitrophenyl L‐L and L‐D dipeptide mixtures obtained on hydrazinolysis of each of the dipeptide‐matrix assemblies. ‘Hydrazinolysis‐HPLC’ has been used also to determine intermediate peptide homogeneity in ultra‐high load solid (gel) phase synthesis with Boc amino acids. Cross‐linked poly(N‐[2‐(4‐hydroxyphenyl)ethyl]acrylamide) and two derived polymers incorporating spacer groups have been used as supports. The spacer groups made possible peptide C‐terminal attachment by either HF‐labile benzyl ester or HF‐labile cyclohexyl ester bonds, while still incorporating the phenolic ester linkage susceptible to rapid hydrazinolytic scission.

Synthesis and characterisation of porous polymers

Sherrington

1993

State‐of‐the‐art electron microscopic studies have been made of the ultrastructure of a matrix of specifically prepared styrene‐divinylbenzene resin sorbents. Image analysis methods have been applied to quantify the porous morphology of these resins in the “dry”, “freeze‐dried” and “frozen” states. Significant swelling has been demonstrated in the wet state. Highly porous Polyhipe® monoliths have been prepared and used to produce a polyamide‐impregnated composite support for use in solid phase synthesis of peptides. The composite shows good pressure resistance and allows high yields of pure peptides to be achieved. Polyhipe® polymers with very high surface areas (up to 350 m2g−1) have been prepared by applying the methodologies of porous particulate resin production to achieve highly porous walls in the Polyhipe® structures. Finally, novel procedures are described for the preparation of porous particulate polyimides and polybenzimidazoles involving a paraffin oil dispersion methodology. These thermooxidatively stable resins have been prepared with modest surface areas of ∼30 m2g−1 and offer good prospects for use as supports for alkene transition metal complex oxidation catalysts.