Malaysian Journal of Analytical Sciences Vol 25 No 6 (2021): 940 - 948

 

 

 

 

CONJUGATION OF TERNATIN BIOMOLECULE WITH POLYETHYLENE GLYCOL ENHANCED CONJUGATES SOLUBILITY AND STABILITY: SYNTHESIS AND PHYSICOCHEMICAL CHARACTERISATION

 

(Konjugasi diantara Molekul Ternatin dan Polietilena Glikol dengan Penambahbaikan Sifat Keterlarutan dan Kestabilan: Sintesis dan Pencirian Fizikokimia)

 

Nurul Aina Jamaludin and Noor Faizah Che Harun*

 

Green Chemistry and Sustainable Engineering Technology, Polymer Engineering Technology Section,

Universiti Kuala Lumpur, Branch Campus Malaysian Institute of Chemical and Bioengineering Technology,

78000 Alor Gajah, Melaka, Malaysia

 

*Corresponding author:  noorfaizah@unikl.edu.my

 

 

Received:  15 September 2021; Accepted: 29 October 2021; Published:  27 December 2021

 

 

Abstract

Ternatin, a highly N-methylated cyclic heptapeptide has promising potential for cancer treatment. However, its efficiency in biological treatment is limited due to its poor solubility and high degradation in aqueous solution. In this present study, methoxy polyethylene glycol (mPEG)-ternatin conjugate abbreviated as mPEG-ternatin was synthesised by direct esterification between a carboxyl end group of methoxy polyethylene glycol, mPEG-COOH and a hydroxyl group in the β-position of ternatin biomolecule which enhanced its solubility and decreased the degradation of ternatin biomolecule in aqueous solution while retaining its inherent anticancer properties. To this end, mPEG-ternatin linked through ester bond was further confirmed using various analytical techniques including FTIR, UV-Vis spectroscopy and HPLC. Importantly, in the solubility and stability studies, the solubility of mPEG-ternatin conjugate was found to be 8% higher than unconjugated ternatin. Furthermore, mPEG-ternatin conjugate exhibited a decreasing percentage of degradation of ternatin biomolecule by 1.9-fold lower than unconjugated ternatin after incubation in 10 mM HEPES pH 7.4 buffer solution at 37 °C for 6 hours. Ultimately, the enhanced properties of ternatin biomolecule by conjugating with a mPEG segment is expected to become new fundamental study in related fields as well as provide new insight into cancer treatments.

 

Keywords:  polyethylene glycol, ternatin, conjugation, esterification, solubility

 

Abstrak

Ternatin, dengan kandungan N-metil siklik heptapeptida yang tinggi mempunyai potensi untuk rawatan kanser. Walau bagaimanapun, keberkesanannya terbatas dalam rawatan biologi disebabkan rendah keterlarutan dan kestabilannya di dalam air. Dalam kajian ini, konjugat diantara metoksi polietilena glikol (mPEG) dan ternatin, mPEG-ternatin telah disediakan melalui proses pengesteran secara langsung diantara kumpulan karboksil dari metoksi polietilena glikol, mPEG-COOH dan kumpulan hidroksil di posisi β dalam biomolekul ternatin. Hal ini demikian, untuk meningkatkan keterlarutan dan kestabilan molekul ternatin di dalam larutan akues tanpa mengganggu sifat anti kansernya. PEG-ternatin yang dihubungkan melalui ikatan ester disahkan melalui pelbagai teknik analisa yang telah dilakukan iaitu FTIR, spektroskopi UV-Vis dan HPLC. Hasil daripada kajian ini, keterlarutan biomolekul ternatin di dalam konjugat PEG-ternatin didapati ⁓8% lebih tinggi daripada molekul ternatin bebas. Sementara itu, melalui ujian kestabilan konjugat, PEG-ternatin menunjukkan penurunan peratusan degradasi molekul Ternatin sebanyak 1.9 kali ganda lebih rendah daripada molekul ternatin bebas. Kesimpulannya, penambahbaikan sifat molekul ternatin dengan kaedah konjugasi secara terus dengan molekul mPEG akan memberikan peluang baru dalam rawatan kanser.

 

Kata kunci:  polietilena glikol, ternatin, konjugat, esterifikasi, keterlarutan, kestabilan

 

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