Side chain-to-Side chain Cyclization by Intramolecular Click Reaction - Building Blocks, Solid Phase Synthesis and Conformational Characterization
Side chain-to-side chain cyclization is frequently employed to stabilize and select specific conformations and to reduce susceptibility toward proteolytic degradation. Among the numerous modes of cyclization bioisosteric modifications that can be accomplished without elaborate orthogonal protection schemes are of great interest. The recently introduced CuI-catalyzed azide—alkyne 1,3-dipolar Huisgen's cycloaddition  as a prototypic “Click reaction”  presented a promising opportunity to develop a new paradigm for intramolecular side chain-to-side chain cyclization. The inherent high energetics, chemical selectivity, and the demonstrated bioorthogonal characteristics of the azide and alkynyl functions, as well as the proteolytic stability, and the peptidomimetic nature of the cycloaddition product, the 1,4-disubstituted [1,2,3]triazolyl moiety, suggest that 1,4-bridged [1,2,3]triazolyl-mediated side chain-to side chain cyclization could offer an interesting mode of...
KeywordsCyclic Peptide Lactam Ring Cycloaddition Product Chain Cyclization Triazole Moiety
The work was funded by FIRB internazionalizzazione 2005 RBIN04TWKN.