Peptide synthesis on the new polyoxyethylene‐polystyrene graft copolymer, synthesis of insulin B 21–30

Abstract

An insoluble graft copolymer composed of the covalently bound polyoxyethylene to cross‐linked polystyrene‐divinylbenzene was employed as the solid support for peptide synthesis. The physical properties of this new polymeric support were similar to those of the cross‐linked polystyrene. Thus, identical manipulations such as shaking and filtration could be performed on this resin. The graft copolymer was used for the synthesis of the C‐terminal decapeptide of bovine insulin B‐chain in the usual solid‐phase manner. The protected peptide was cleaved from the polymeric support by photolysis and was purified by chromatography on silica gel and Sephadex LH‐20. Samples of the decapeptide were treated with liquid HF and the unprotected peptide was purified by ion‐exchange chromatography. The free peptide was shown to be homogeneous by HPLC, electrophoresis and t.l.c. The identity of this peptide was also confirmed by FAB‐MS and amino acid analysis. The synthesized peptides were shown to be free of racemization. The free peptide possesses a disordered conformation as revealed by the CD measurement.

Polymer‐Peptide Block Copolymers – An Overview and Assessment of Synthesis Methods

“…In the early 1980s a simple method of using solid phase peptide synthesis (SPPS) to access peptide‐polymer block copolymers was developed by the groups of Mutter and Bayer 25–27. PS beads that were regularly used for SPPS were loaded with amino‐terminated poly(ethylene glycol) (PEG) via an acid labile benzyl‐ether linker.…”

Synthesis of Macromolecules Containing Phenylalanine and Aliphatic Building Blocks

“…The fourth hypothesis is that the coupling reaction for steps a and c was incomplete due to aggregation of the growing chain. Few conditions to overcome this potential problem of aggregation were evaluated including (1) reducing the loading density on the resin, i.e., the targeted loading of the resin with the first phenylalanine residue was half (Table , entry 5; Figure S4, entry 5, Supporting Information), (2) improving the solvation of the growing chain by either adding dichloromethane, i.e., 1/1 DMF/CH 2 Cl 2 (Table , entry 6; Figure S4, entry 6, Supporting Information), as CH 2 Cl 2 has a superior capacity to swell the resin as compared to DMF, or adding chaotropic salts such as lithium chloride (Table , entry 7; Figure S4, entry 7, Supporting Information), (3) conducting steps a and c under microwave irradiations (Table , entry 8; Figure S4, entry 8, Supporting Information), or (4) using a Tentagel resin (Table , entry 9; Figure S4, entry 9, Supporting Information) that is reported to have a kinetic behavior of its reactive sites similar to those in solution chemistry. None of the attempts conducted to noticeable positive changes.…”

Preparation of tri(ethylene glycol) grafted core‐shell type polymer support for solid‐phase peptide synthesis

“…[8][9][10][11][12][13] Poly(ethylene glycol) (PEG) grafted PS resins such as TentaGel ® , Amphispheres™, and Hypogel ® are developed for SPPS as an amphiphilic solid supports. [8][9][10] As the grafted PEG improves compatibility of the resin with hydrophilic solvents including aqueous media, those resins have been widely used as a polymer support for on-bead peptide synthesis and on-bead bioassays. However, the problem of the broadly distributed functional groups still remains, which might cause low efficiency in some reactions.…”

“…Additionally, we synthesized NPY [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] amide (H-DNPGEDAPAED-MARY-NH 2 ) and NPY [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] amide (H-YSALRHYINLITRQRY-NH 2 )…”