Deletion of Ac-NMePhe(1) from [NMePhe(1) ]arodyn under acidic conditions, part 1: effects of cleavage conditions and N-terminal functionality.
Deletion of Ac-NMePhe(1) from [NMePhe(1) ]arodyn under acidic conditions, part 1: effects of cleavage conditions and N-terminal functionality.
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DOI：
10.1002/bip.21496
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发表时间：
2011
期刊：
影响因子：
2.9
通讯作者：
Aldrich, Jane V.
中科院分区：
文献类型：
--
作者：
Fang, Wei-Jie;Bennett, Marco A.;Aldrich, Jane V.
Peptides containing N-methylamino acids can exhibit improved pharmacodynamic and pharmacokinetic profiles compared to nonmethylated peptides, and therefore interest in these N-methylated peptides has been increasing in recent years. Arodyn (Ac[Phe1,2,3,Arg4,D-Ala8]Dyn A(1–11)-NH2) is an acetylated dynorphin A (Dyn A) analog that is a potent and selective κ opioid receptor antagonist (Bennett et al. J. Med. Chem. 2002, 45, 5617), and its analog [NMePhe1]arodyn shows even higher affinity and selectivity for κ opioid receptors (Bennett et al., J. Pep. Res. 2005, 65, 322). During the synthesis of [NMePhe1]arodyn analogs, the arodyn (2–11) derivatives were obtained as major products. Analysis indicated that Ac-NMePhe was lost from the completed peptide sequence during acidic cleavage of the peptides from the resin and that the acetyl group played an important role in this side reaction. Different cleavage conditions were evaluated to minimize this side reaction and maximize the yield of pure [NMePhe1]arodyn analogs. Modifications to the N-terminus of the peptides to prevent the side reaction were also explored. The incorporation of a heteroatom-containing group such as methoxycarbonyl as the N-terminal functionality prevented this side reaction, while the incorporation of a bulky acyl group could not. Substituting NMePhe with the conformationally constrained analog Tic (1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) also prevented the side reaction.
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DOI：
10.1111/j.1399-3011.2005.00216.x
发表时间：
2005-03-01
期刊：
JOURNAL OF PEPTIDE RESEARCH
影响因子：
--
作者：
Bennett, MA;Murray, TF;Aldrich, JV
通讯作者：
Aldrich, JV
影响因子：
2.1
作者：
Biron, E;Chatterjee, J;Kessler, H
通讯作者：
Kessler, H
DOI：
10.1073/pnas.78.10.6543
发表时间：
1981-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
CHAVKIN, C;GOLDSTEIN, A
通讯作者：
GOLDSTEIN, A
影响因子：
2.1
作者：
Jiang, WQ;Pereira-Lima, SMMA;Maia, HLS
通讯作者：
Maia, HLS
DOI：
10.1111/j.1399-3011.2004.00213.x
发表时间：
2005-02-01
期刊：
JOURNAL OF PEPTIDE RESEARCH
影响因子：
--
作者：
Teixidó, M;Albericio, F;Giralt, E
通讯作者：
Giralt, E