Click Chemistry Building Blocks for Peptide Synthesis
K. Barry Sharpless first elucidated the principles of CLICK chemistry in 2001 . He enumerated a number of characteristics that CLICK reactions should have, including:
• give very high chemical yields
• generate only inoffensive byproducts
• be stereospecific
• exhibit a large thermodynamic driving force > 84 kJ/mol to favor a reaction with a single reaction product.
He also proposed that CLICK chemistry processes should:
• have simple reaction conditions
• use no solvent or use a solvent that is benign or easily removed (preferably water)
• provide simple product isolation by non-chromatographic methods (crystallization or distillation)
In 2002, K. Barry Sharpless and Morton Mendel independently reported the copper-catalyzed Huisgen azide alkyne 1,3-cycloaddition reaction which fulfilled most of the requirements for CLICK chemistry. Although there are many other reactions that fulfill the requirements for click reactions, this reaction has become synonymous with click chemistry.
The Cu(I) catalyzed cycloaddition reaction generates exclusively 1,4-substituted 1,2,3-triazoles. Utilization of a ruthenium catalyst provides the complimentary 1,5-disubstituted triazoles.
The high yields and easy, rapid purification of the peptide products make click chemistry a useful methodology for preparing radio-labeled peptides for applications such as PET imaging. Click chemistry has been used in peptide cyclization , DNA-peptide conjugation , fluorescent dye labeling and surface immobilization of peptides. Recently, stapled peptides have been prepared utilizing click chemistry to form the “staple”.
The cycloaddition reaction can be performed while the peptide is still attached to the resin or in solution following cleavage.
Click chemistry utilizing the Cu(I) catalyzed Huisgen cycloaddition between an azide and an alkyne is a convenient way of preparing tagged peptides and cyclized peptides. The azides and alkynes do not need protecting groups during peptide synthesis by either Fmoc or Boc protocols. The post synthetic modification of the peptide can be performed directly, in high yield, without selective deprotection schemes.
AAPPTec provides high purity click chemistry reagents at very competitive prices. AAPPTec can provide click chemistry reagents in bulk quantities. To inquire about bulk pricing, please send an e-mail to sales@aapptec.com.
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