MODULASI JUNCTION ANTAR SEL MENGGUNAKAN PEPTIDA KADHERIN: UPAYA MENINGKATKAN PENGHANTARAN OBAT

Ernawati Sinaga1, Seetharama D.S. Jois2, Mike Avery2, Irwan Makagiansar2,
Usman S.F. Tambunan3, dan Teruna J. Siahaan2
1. Fakultas Biologi, Universitas Nasional, Jakarta 12520, Indonesia
2. Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66047 USA
3. Departemen Kimia, FMIPA, Universitas Indonesia, Depok 16424, Indonesia

Abstrak

Banyak senyawa protein, peptida dan peptidomimetik yang ditemukan akhir-akhir ini memiliki potensi terapeutik yang besar, namun terhambat aplikasinya sebagai obat karena mengalami masalah penghantaran ke situs sasarannya (drug delivery). Dalam beberapa tahun belakangan ini telah dikembangkan satu metode baru dalam modulasi junction antar sel menggunakan senyawa-senyawa peptida kadherin, yaitu peptida yang sekuensnya diturunkan dari sekuens fragmen peptida yang terdapat pada situs pengikatan kadherin. Dalam penelitian ini telah dievaluasi aktivitas beberapa peptida kadherin dalam memodulasi junction antar sel. Hasilnya menunjukan bahwa peptida-peptida Ac-LFSHAVSSNG-NH2 (HAV-10), Ac-SHAVSS-NH2 (HAV-6), Ac-QGADTPPVGV-NH2 (ADT-10), dan Ac-ADTPPV-NH2 (ADT-6) memiliki aktivitas yang cukup tinggi dalam memodulasi junction antar sel-sel MDCK (Madin Darby Canine Kidney). Hasil penelitian ini telah memberikan sumbangan yang berarti dalam pemantapan suatu metoda baru dalam penghantaran obat melalui modulasi junction antar sel menggunakan senyawa-senyawa peptida kadherin.

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Abstract

Modulation of Intercellular Junction by Utilization of Cadherin Peptides as an Effort to Improve Drug Delivery.

Rapid advances in combinatorial chemistry and molecular biology has influenced the discovery of many proteins, peptides and peptidomimetics as potential therapeutic agents. Unfortunately, the practical application of these potential drugs is often restricted by the difficulties of delivering them to target site(s) due to the presence of biological barriers. Recently, a new method to improve the drug delivery, that is by modulating the intercellular junction, has been evaluated. Modulation of intercellular junction could be achieved by modulating the proteins which play important role in establishing the intercellular junction, one of which is cadherin. In the present work we have demonstrated the ability of several cadherin peptides, i.e. Ac-LFSHAVSSNG-NH2 (HAV-10), Ac-SHAVSS-NH2 (HAV-6), Ac-QGADTPPVGV-NH2 (ADT-10), and Ac-ADTPPV-NH2 (ADT-6) to modulate the intercellular junction of MDCK (Madin Darby Canine Kidney) cells, this finding is a contribution to the establishment of a new method to improve the drug delivery by utilization of cadherin peptides by modulating the intercellular junction.

Keywords: Intercellular junction, peptide, cadherin, drug delivery, MDCK cells

Dipublikasi dalam: MAKARA SAINS, VOL. 8, NO. 1, APRIL 2004: hal. 25-34