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Modular Solid‐Phase Synthesis of Teroxazoles as a Class of α‐Helix Mimetics
Author(s) -
Pinto Gomes Cristiano,
Metz Alexander,
Bats Jan W.,
Gohlke Holger,
Göbel Michael W.
Publication year - 2012
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201200339
Subject(s) - peptidomimetic , chemistry , solid phase synthesis , helix (gastropod) , protein design , scaffold , modular design , combinatorial chemistry , oxazole , stereochemistry , protein structure , peptide , biochemistry , computer science , ecology , database , snail , biology , operating system
α‐Helices are ubiquitous structural elements of proteins and are important in molecular recognition. Small molecules mimicking α‐helices have proven to be valuable biophysical probes or modulators of protein‐protein interactions. Here, we present modeling studies and the modular solid‐phase synthesis of teroxazole derivatives as a new class of α‐helix mimetics. The synthesis is compatible with a variety of functional groups and should thus be generally applicable for generating diversely substituted oligo‐oxazole scaffolds. The teroxazole scaffold is predicted to be polar and to project peptidomimetic side chains at positions i , i +3, and i +6 of an α‐helix, which complements projection patterns of existing helix mimetics. The scaffold retains sufficient conformational flexibility to conform to induced‐fit models of protein‐protein interaction inhibition.