Protein chemical synthesis usually relies on the use of native chemical ligation that couples peptide thioester with a Cys-peptide. A limitation of this method is the difficulty of finding an appropriate Cys ligation site in many synthetic targets. To overcome this problem, the ligation-desulfurization approach has been developed. This approach involves the use of a thiol-containing amino acid as the ligation partner. After the sequence assembly is completed, the thiol group is removed through a desulfurization reaction to generate the standard amino acids. Currently this strategy has been applied to the ligations at a number of amino acids including Ala, Phe, Val, Lys, Thr, Leu, Pro and Gin. The present article reviews the design and svnthesis of these thiol-containing amino acids for native chemical libation at non-Cys sites.
Cyclotides constitute a fascinating family of circular proteins containing ca.30 amino acid residues.They have a unique cyclic cysteine knot topology and exhibit remarkable thermal,chemical and enzymatic stabilities.These characteristics enable them to have a range of biological activities and promising pharmaceutical and agricultural applications.Here,we present a practical strategy for the chemical synthesis of cyclotides through the intramolecular ligation of fully unprotected peptide O-esters.This strategy involves the mild Fmoc solid-phase peptide synthesis of the peptide O-ester backbone,the head-to-tail cyclization of the cyclotide backbone by native chemical ligation,and the oxidative refolding to yield the natural knot protein.The simplicity and high efficiency of the strategy can be employed in the synthesis of artificial cyclotides for pharmaceutical applications.
Cyclotides constitute a fascinating family of circular proteins containing ca.30 amino acid residues.They have a unique cyclic cysteine knot topology and exhibit remarkable thermal,chemical and enzymatic stabilities.These characteristics enable them to have a range of biological activities and promising pharmaceutical and agricultural applications.Here,we present a practical strategy for the chemical synthesis of cyclotides through the intramolecular ligation of fully unprotected peptide O-esters.This strategy involves the mild Fmoc solid-phase peptide synthesis of the peptide O-ester backbone,the head-to-tail cyclization of the cyclotide backbone by native chemical ligation,and the oxidative refolding to yield the natural knot protein.The simplicity and high efficiency of the strategy can be employed in the synthesis of artificial cyclotides for pharmaceutical applications.
