Synthesis of gramicidin S and its analogues via an on-resin macrolactamization assisted by a predisposed conformation of the linear precursors.
A simple and efficient preparation of gramicidin S and its analogues is described. It involves solid-phase peptide synthesis and on-resin macrolactamization without side chain protection, affording cyclic products in high yield and high purity. The high specificity of the cyclization reaction was shown to originate in the formation of a pre-organized conformation of the linear biosynthetic precursor of gramicidin S. This facile method will provide convenient access to the analogues of the natural product for functional optimization to counter microbial resistance.
Bu
Xianzhang
X
Department of Chemistry and Biotechnology Research Institute, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China.
Wu
Xiaoming
X
Ng
Na Lee Joyce
NL
Mak
Chun Kit
CK
Qin
Chuanguang
C
Guo
Zhihong
Z
D000409:Alanine / Q000138:chemical synthesis; D000595:Amino Acid Sequence; D020650:Combinatorial Chemistry Techniques; D006096:Gramicidin / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D007769:Lactams; D008968:Molecular Conformation; D011498:Protein Precursors / Q000737:chemistry; D012116:Resins, Plant
D007769:Lactams; D011498:Protein Precursors; D012116:Resins, Plant; D006096:Gramicidin; D000409:Alanine