Synthesis of cyclo-PLAI using a combination of solid- and solution-phase methods Orin Inggriani Napitupulu Dadan Sumiarsa Toto Subroto Nurlelasari Desi Harneti Unang Supratman Rani Maharani 10.6084/m9.figshare.7583072.v1 https://tandf.figshare.com/articles/journal_contribution/Synthesis_of_cyclo-PLAI_using_a_combination_of_solid-_and_solution-phase_methods/7583072 <p>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/<i>t</i>-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, <sup>1</sup>H-NMR, <sup>13</sup>C-NMR, and compared with previously reported spectral data for the cyclic product.</p> 2019-04-02 12:39:37 Cyclo-PLAI cyclotetrapeptide HATU cyclization solid-phase peptide synthesis 2-chlorotrityl resin