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Molecular‐Size Reduction of a Potent CXCR4‐Chemokine Antagonist Using Orthogonal Combination of Conformation‐ and Sequence‐Based Libraries
Author(s) -
Fujii Nobutaka,
Oishi Shinya,
Hiramatsu Kenichi,
Araki Takanobu,
Ueda Satoshi,
Tamamura Hirokazu,
Otaka Akira,
Kusano Shuichi,
Terakubo Shigemi,
Nakashima Hideki,
Broach James A.,
Trent John O.,
Wang Zixuan,
Peiper Stephen C.
Publication year - 2003
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.200351024
Subject(s) - pentapeptide repeat , antagonism , alanine , sequence (biology) , stereochemistry , antagonist , chemistry , confusion , computer science , combinatorial chemistry , computational biology , biology , biochemistry , amino acid , peptide , psychology , receptor , psychoanalysis
Efficient downsizing of peptides : By combination of two orthogonal “conformation‐based” and “sequence‐based” libraries, the cyclic pentapeptide cyclo (‐ L ‐Nal 1‐Gly 2‐ D ‐Tyr 3‐ L ‐Arg 4‐ L ‐Arg 5‐) (Nal= L ‐3‐(2‐naphthyl)alanine; see overlay of the five lowest energy structures), which exhibited strong CXCR4 antagonism (IC 50 =4 n M ) comparable to that of a 14‐residue lead compound, T140, was discovered.