Converting polar cyclic peptides into membrane permeable molecules using N-methylation

被引：7

作者：

Lee, Leo L. H. ^{[1
]}

Buckton, Laura K. ^{[1
]}

McAlpine, Shelli R. ^{[1
]}

机构：

[1] Univ New South Wales, Chem, Sydney, NSW, Australia

来源：

PEPTIDE SCIENCE | 2018年 / 110卷 / 03期

基金：

英国医学研究理事会;

关键词：

cell permeability; cyclic peptides; N-methyl; peptide; AMINO-ACIDS; CELL-PERMEABILITY; BIOLOGICAL-ACTIVITY; PHASE SYNTHESIS; SOLID SUPPORT; AMIDE BONDS; ANALOGS; SOLUBILITY; SCAFFOLDS; DESIGN;

D O I：

10.1002/pep2.24063

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Described are the design, synthesis, and biological evaluation of 5 N-methylated analogs that are based on a lead drug structure LB51. LB51 is a cyclic pentapeptide that inhibits heat shock protein 90 and although a potent inhibitor of the protein function, it has poor cell permeability. Introduction of an N-methyl moiety at each amino acid produces 5 analogs of LB51, where all 5 show significantly improved membrane permeability over the lead molecule despite the presence of 4 highly polar side chains.

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页数：10

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