Tertomotide 유래 옥타펩타이드의 항염증 활성
Anti-inflammatory activities of octapeptides derived from tertomotide
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초록
Tertomotide는 hTert의 일부분이며 항암 백신으로 개발된 펩타이드이나 임상시험과 동물실험에서 염증성 질환을 개선하는 활성이 다수 보고된 바 있다. 다양한 연구에서 발견된 항염활성에도 불구하고 약물성이 높지 않아 일반적인 항염약물로의 개발이 어렵다. 다양한 부위에서 일어나는 염증성 증상에 활용하기 위해서는 항염활성과 약물성이 동반되어야 하므로 구조의 개선이 필요하다. 본 연구에서는 tertomotide의 구조를 기반으로 12 종의 옥타펩타이드를 설계하고 항염증 활성을 측정하여 약물성이 개선된 tertomotide 유래의 항염 펩타이드를 도출하고자 하였다. 이를 위해 활성화된 단핵구에서 염증성 cytokine인 TNF-α의 분비에 미치는 영향을 측정하여 각 펩타이드의 항염 활성을 평가하였고 양성대조군으로 비교한 estradiol이나 tertomotide 이상의 항염활성을 가진 펩타이드를 도출하였다. 본 연구의 결과는 tertotmotide 유래 펩타이드들을 활용한 신규 항염증 소재 개발 연구에 도움이 될 것으로 예상되며, 항염증 활성 등의 생리활성이 있으나 약물성이 낮은 펩타이드에 대해 계산화학적 접근으로 구조를 변경하여 기능적 잠재력 있는 신규활성물질을 도출하는 융합연구의 좋은 예가 될 것으로 사료된다.
Abstract
Tertomotide is a peptide fragment of hTert and developed as a vaccine targeting cancer. It has been reportedly known to ameliorate inflammatory symptoms in clinical tests and in animal studies. However, the therapeutic potential of tertomotide is not supposed to be comparable to conventional anti-inflammatory agents due to low druglikeness In order to treat inflammations present in varous lesion, the structure of tertomotide is required to be modified. In this context, 12 octapeptides were designed based on tertomotide and screened for the anti-inflammatory activity in activated monocyte by measuring TNF-α secretion. As a result, some octapeptides has been exerted anti-inflammatory activity, comparable to or better than tertomotide and estradiol, known anti-inflammatory agents. This result is supposed to be helpful for developing therapeutic purpose exploiting other tertomotide-derived peptides and would be an example for designing novel drug based on active biomolecules with undesirable structure by convergence study of biology and computer-aided medicinal chemistry.
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