Synthesis, characterization, and application of butanediol dimethacrylate cross-linked polystyrene: a flexible support for gel phase peptide synthesis

We have developed a new cross-linked polymeric support by the copolymerization of styrene and butanediol dimethacrylate (BDODMA) for the solid-phase synthesis of peptides. The resin support was synthesized in various cross-linking densities by radical aqueous suspension polymerization. The copolymer was characterized by IR and 13C NMR techniques. The shape, size, and morphological features of the cross-linked polymer bead were analyzed by scanning electron microscopy. PS-BDODMA polymer support showed excellent swelling properties in all types of solvents that are used in solid-phase peptide synthesis (SPPS). The stability of polymer in various reagents and solvents was tested by IR. The polymer does not show any change in its IR spectrum even after 48 h treatment with TFA, 20% piperidine in DMF, aqueous NaOH, hydroxylamine in aqueous MeOH, and liquor ammonia. The resin can be functionalized with chloromethyl, aminomethyl, and hydroxymethyl groups under various reaction conditions. The efficiency of this new support was demonstrated by the synthesis of few model peptides with very high purity and yield. These peptides were characterized by MALDI TOF MS and amino acid analysis

Optimization in peptide synthetic conditions of 1,4-butanediol dimethacrylate cross-linked polystyrene resin and its efficiency in solid phase peptide synthesis

A 1,4-butanediol dimethacrylate cross-linked polystyrene (PS–BDODMA) support was prepared by aqueous suspension polymerization. The C-terminal amino acid incorporation, Nα-Fmoc and Boc-deprotection, acylation reactions and the removal of the target peptide from the support were optimized. The efficiency of the support was demonstrated by synthesizing leucyl-alanyl-glycyl-valine, acyl carrier protein fragment (65–74) and a 25-residue peptide fragment designed from the NS1 region of hepatitis C viral polyprotein under optimal reaction conditions. The efficiency of the polymer support was compared with commercially available Merrifield and Sheppard resins by synthesizing the same peptides under the identical conditions. The purity of these peptides was checked by HPLC and the structures of the peptides were established by amino acid analysis and MALDI TOF MS

Photocleavable 2-nitrobenzylamino anchored polystyrene-butanediol dimethacrylate supports for the synthesis of protected peptides, peptide amides and peptide N-alkyl amides

2-Nitrobenzylamino-type anchoring groups were incorporated on 2% butanediol dimethacrylate cross-linked polystyrene support. The resultant photolabile polymeric supports were used for the synthesis of fully protected peptides and their final cleavage as C-terminal peptide acids, peptide amides and peptide N-alkyl amides by photolysis under mild neutral conditions. The photosensitive chromophore has a dual function of serving as an anchoring linkage between the support and the growing peptide chain and as a latent reagent for the conversion of a C-terminal carboxyl group into the modified form during photolytic cleavage. The C-terminal modified peptides were obtained by irradiating the peptidyl resin in a TFE/DCM mixture at 350 nm. The efficacy of the new resin is illustrated by synthesizing the protected derivatives of the peptides in very high yield and purity. The identity of the peptides was checked by amino acid analysis, TLC and MALDI TOF MS. Synthesis of protected peptides, peptide amides and peptide-N-alkylamide under neutral condition

Synthesis of esculentin-1 antibacterial peptide fragments on 1,4-butanediol dimethacrylate cross-linked polystyrene support

Peptide segments corresponding to antibacterial esculentin-1 (1–15), (33–44), (9–27), and their modified forms were synthesized on 1,4-butanediol dimethacrylate cross-linked polystyrene (PS-BDODMA) support. Hydroxymethyl and aminomethyl 2% PS-BDODMA supports were used for the synthesis. The HMPB linker was appended to the aminomethyl resin using HBTU in presence of HOBt and the first amino acid was incorporated using MSNT. The conventional Fmoc synthetic protocol was used for the synthesis of peptides. The peptides were cleaved from the support using TFA. The peptides were purified by HPLC, and characterized by amino acid analysis and MALDI TOF MS. The secondary structures of the peptides were revealed by CD measurements. The synthesis of these peptides illustrates the utility of the new support for the synthesis of long-chain bioactive peptides. The synthetic peptides were tested for antimicrobial activity against Escherichia coli Mos blue, E. coli 2, Bacillus brevis, B. megaterium, Pseudomonas HTL, and Vibrio mimicus. The antibacterial activity of the peptides was explained on the basis of the helicity and charged nature of the sequences

Synthesis and characterization of glycerol dimethacrylate cross-linked polymethyl methacrylate: a resin for solid phase peptide synthesis

The new glycerol dimethacrylate cross-linked polymethyl methacrylate polymer support (GDMA-PMMA) for solid phase synthesis is presented. The synthesis of GDMA-PMMA resin is based on the cross-linking of GDMA with methyl methacrylate by free radical polymerization, affording a polymer containing ester and secondary hydroxyl groups. The polymer was prepared using benzoyl peroxide as initiator either via bulk polymerization or via suspension polymerization in polyvinyl alcohol, the latter yielding a beaded resin. The polymerization reaction was investigated with respect to the effect of amount of cross-linking agent in order to vary the swelling, loading and the mechanical stability of the resin. The polymer was characterized by FT-IR and 13C CP MAS NMR spectroscopic techniques. The solvent uptake of the polymer was studied in relation to cross-linking and compared with Merrifield resin. The stability of the resin was tested in various synthetic conditions used in solid phase peptide synthesis. The resin was derivatized with chloro and amino functional groups. The C-terminal amino acid incorporation, Nα-Fmoc deprotection, acylation reactions and removal of target peptide from the support were optimized. The efficiency of the resin was demonstrated by synthesizing leucyl-alanyl-glycil-valine, alanine-alanine-alanine-alanine, acyl carrier protein (65–74) and retro-acyl carrier protein (74–65) fragments under optimal conditions and is compared with Merrifield resin. The purity of the peptides was checked by HPLC and identities were established by amino acid analysis and mass spectroscopic techniques