Synthesis of cyclo-PLAI using a combination of solid- and solution-phase methods

Abstract

Cyclo-PLAI was successfully synthesized using a combination of solid- and solution-phase methods. This current synthesis was found to be faster than the previously reported synthesis for the cyclic peptide. The linear precursor was synthesized on 2-chlorotrityl resin with Fmoc/t-Bu strategy. HATU/HOAt was employed as the coupling reagent in the amide bond formation on the resin. Cyclization of the linear precursor was experimented with HATU/HOAt reagents with different conditions. However, the linear precursor was best cyclized using HATU reagent in DIPEA by stirring the reaction mixture at 0 °C for 1 h and followed by stirring the reaction mixture at room temperature for 30 min, giving the cyclic product in 70% yield (calculated from the linear peptide). Both linear and cyclic products were characterized using HR-TOF-ESMS, ¹H-NMR, ¹³C-NMR, and compared with previously reported spectral data for the cyclic product.

Graphical Abstract

KEYWORDS:

• Cyclo-PLAI
• cyclotetrapeptide
• HATU cyclization
• solid-phase peptide synthesis
• 2-chlorotrityl resin

Additional information

Funding

RM would like to thank to research grants of Kemenristek DIKTI (PBK Scheme) and ALG research grant-Unpad (Prof. Unang Supratman and Prof. Toto Subroto) for financial support.