TY - JOUR

T1 - High capacity poly(ethylene glycol) based amino polymers for peptide and organic synthesis

AU - Roice, Michael

AU - Johannsen, Ib

AU - Meldal, Morten

PY - 2004/10

Y1 - 2004/10

N2 - A beaded, chemically stable, high capacity amino resin for solid phase synthesis under polar and non-polar conditions is described. By exhaustive reduction of amide carbonyl groups in PEG cross linked poly(ethylene glycol)-poly(-acrylamide) copolymer (PEGA) a significant increase in functional amino groups is obtained. Furthermore, a resin containing 90% PEG which is free of amide carbonyl groups is produced. The polymer was characterized by IR spectroscopy and the macroscopic properties of the beads were analyzed by microscopy. Excellent swelling properties in various solvents ranging from water to DCM were demonstrated. The chemical stability of the polymer in various reagents and solvents was investigated and changes in resin properties monitored by IR spectroscopy. The mechanical stability of the resin was analyzed by measurement of compressive strain. The unique three dimensional structure of the swelled polyethylene glycol network facilitate fast and unhindered diffusion of reagents and the support is excellent for synthesis of peptides or peptide mimetics, which can be produced in high yield/reaction volume. The efficacy of the new resin in solid phase synthesis was demonstrated by synthesizing an α-MSH peptide fragment. A cyclic peptide mimetic was also synthesized on the new resin by the Cu (1) catalyzed intra molecular cyclo addition of alkyne and azide to form a triazole acting as a disulphide mimetic entity in very high yield and purity.

AB - A beaded, chemically stable, high capacity amino resin for solid phase synthesis under polar and non-polar conditions is described. By exhaustive reduction of amide carbonyl groups in PEG cross linked poly(ethylene glycol)-poly(-acrylamide) copolymer (PEGA) a significant increase in functional amino groups is obtained. Furthermore, a resin containing 90% PEG which is free of amide carbonyl groups is produced. The polymer was characterized by IR spectroscopy and the macroscopic properties of the beads were analyzed by microscopy. Excellent swelling properties in various solvents ranging from water to DCM were demonstrated. The chemical stability of the polymer in various reagents and solvents was investigated and changes in resin properties monitored by IR spectroscopy. The mechanical stability of the resin was analyzed by measurement of compressive strain. The unique three dimensional structure of the swelled polyethylene glycol network facilitate fast and unhindered diffusion of reagents and the support is excellent for synthesis of peptides or peptide mimetics, which can be produced in high yield/reaction volume. The efficacy of the new resin in solid phase synthesis was demonstrated by synthesizing an α-MSH peptide fragment. A cyclic peptide mimetic was also synthesized on the new resin by the Cu (1) catalyzed intra molecular cyclo addition of alkyne and azide to form a triazole acting as a disulphide mimetic entity in very high yield and purity.

KW - Cyclo-addition

KW - High loading

KW - PEG-based resin

KW - Peptide mimetics

KW - Solid phase synthesis

UR - http://www.scopus.com/inward/record.url?scp=8844268400&partnerID=8YFLogxK

U2 - 10.1002/qsar.200420021

DO - 10.1002/qsar.200420021

M3 - Journal article

AN - SCOPUS:8844268400

VL - 23

SP - 662

EP - 673

JO - Molecular Informatics

JF - Molecular Informatics

SN - 1868-1743

IS - 8

ER -