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Converting polar cyclic peptides into membrane permeable molecules using N ‐methylation
Author(s) -
Lee Leo L. H.,
Buckton Laura K.,
McAlpine Shelli R.
Publication year - 2018
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.533
H-Index - 7
ISSN - 2475-8817
DOI - 10.1002/pep2.24063
Subject(s) - cyclic peptide , pentapeptide repeat , methylation , chemistry , moiety , membrane , membrane permeability , side chain , molecule , cell permeability , amino acid , polar , biophysics , stereochemistry , cell membrane , biochemistry , combinatorial chemistry , peptide , biology , organic chemistry , physics , astronomy , gene , polymer
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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