Sintesis Heksapeptida Siklik Analog Pipecolisporin sebagai Kandidat Antimalaria
Abstract
Abstract. Malaria remains a global challenge with a significant increase in cases in various countries, including Indonesia. The resistance of Plasmodium falciparum to conventional antimalarial drugs has created an urgent need for new effective therapies. This study aims to synthesize cyclic hexapeptide analogs based on pipecolisporin (Ile – β-Ala – Trp – Pip – Arg – Pro) as potential antimalarial candidates. The method employed combines Solid Phase Peptide Synthesis (SPPS) to produce linear hexapeptides and Liquid Phase Peptide Synthesis (LPPS) for cyclization. The HATU-HOAt reagent was chosen for its ability to enhance efficiency and reduce the risk of epimerization during synthesis. The analog structure was designed by substituting leucine (Leu) residues with arginine (Arg) to optimize the balance between cationic properties and hydrophobicity relevant to antimalarial activity. The synthesis was carried out until the target compound was obtained, which was then characterized using HR-ToF-MS mass spectrometry, showing the presence of a molecular ion peak at m/z [M+H]+ 735.5688, corresponding to the calculated mass of m/z [M+H]+ 734.90. The results of the study demonstrate that pipecolisporin analogs can be successfully synthesized using this combined method.
Abstrak. Penyakit malaria masih menjadi tantangan global dengan peningkatan angka kasus yang signifikan di berbagai negara, termasuk Indonesia. Resistensi Plasmodium falciparum terhadap obat antimalaria konvensional menimbulkan kebutuhan mendesak akan terapi baru yang efektif. Penelitian ini bertujuan untuk mensintesis analog heksapeptida siklik berbasis pipecolisporin (Ile – β-Ala – Trp – Pip – Arg – Pro) sebagai kandidat antimalaria. Metode yang digunakan adalah kombinasi Solid Phase Peptide Synthesis (SPPS) untuk membentuk heksapeptida linier dan Liquid Phase Peptide Synthesis (LPPS) untuk proses siklisasi. Reagen HATU-HOAt dipilih karena kemampuannya meningkatkan efisiensi dan mengurangi risiko epimerisasi selama sintesis. Struktur analog dirancang dengan substitusi residu leusin (Leu) menjadi arginin (Arg) untuk meningkatkan keseimbangan antara sifat kationik dan hidrofobisitas yang relevan dengan aktivitas antimalaria. Sintesis dilakukan hingga diperoleh senyawa target, yang kemudian dikarakterisasi menggunakan spektrometri massa HR-ToF-MS menunjukkan adanya puncak ion molekul pada m/z [M+H]+ 735.5688, yang sesuai dengan massa yang dihitung pada m/z [M+H]+ 734.90. Hasil penelitian menunjukkan bahwa analog pipecolisporin dapat disintesis dengan baik menggunakan metode kombinasi tersebut.
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