Abstract:
PURPOSE: Provided is a method for measuring the substrate specificity of the protease without involving additional separation and purification of the protease and synthesis of a substrate peptide, thereby simply and cheaply carrying out the gene sequencing of the protease. CONSTITUTION: A plasmid pADH-kex2 contains a kex2 gene downstream to an ADH promoter. A plasmid pADH-SteSubInv contains cDNA which encodes a portion containing a golgi apparatus target signal region and a transmembrane region of a golgi apparatus protein of yeast, Ste13, a recognition site of alpha-factor of yeast being known as a substrate of kex2, and a fusion protein containing an invertase of yeast, and which is positioned downstream of the ADH promoter. The method for measuring the substrate specificity of the protease comprises the steps of: (i) constructing a vector containing a gene encoding a protease; (ii) constructing a vector containing a gene encoding a golgi apparatus target signal region and a transmembrane region of a membrane protein in a golgi apparatus of yeast, a gene encoding a substrate region having a specific amino acid sequence, and a gene encoding an invertase of yeast; (iii) producing a transformant by significantly transforming yeast mutant suc2 with the two vectors; and (iv) culturing the transformant in a medium containing sucrose as a sole carbon source and measuring survival rate of the transformant.
Abstract:
The present invention relates to a decoy peptide or polypeptide consisting of a peptide sequence represented by General Formula I below: X_1-Ala-X_2-X_3-Ile-Glu-X_4 (I) wherein X_1 is 0-50 amino acid residues; X_2 is Ser, Glu, or Asp; X_3 is Thr, Glu, or Asp; X_4 is 0-50 amino acid residues; X_2 is not Ser when X_3 is Thr; and the decoy peptide or polypeptide inhibits protein phosphatase 1 (PP1) - mediated dephosphorylation of phospholamban (PLB) through competitive inhibition. It is noteworthy that the decoy peptide or polypeptide of the present invention significantly increases the phosphorylation level of PLB by inhibiting PP1-mediated dephosphorylation. Further, the decoy peptide or polypeptide provides cardio-protective effects by restoring of SERCA2a activity and inotropic effect of enhancing myocardial contractility. The present invention can contribute to the prevention or treatment of PLB-associated diseases.
Abstract:
본 발명은 다음의 단계를 포함하는 심부전(heart failure), 섬유증 또는 염증 치료제의 스크리닝 방법에 관한 것이다: (a) Eya2(eyes absent 2) 유전자를 포함하는 세포에 시험물질을 처리하는 단계; 및 (b) 상기 Eya2 유전자의 발현을 분석하는 단계, 상기 시험물질이 Eya2 유전자의 발현을 증가시키면 심부전, 섬유증 또는 염증 예방 또는 치료제로 판단한다. 본 발명에 따르면, 본 발명은 심부전, 섬유증 또는 염증 예방 또는 치료제의 스크리닝 방법을 제공하며 Eya2 과발현은 장기간 압력과부하 하에서 심장의 섬유증 및 염증뿐 아니라, 심벽 약화, 심실 확장 및 심장 기능의 악화를 억제할 수 있다. 또한, Eya2 유전자를 유효성분으로 포함하는 본 발명의 조성물은 심부전, 섬유증 또는 염증 예방 또는 치료에 효과적이다.
Abstract:
The present invention relates to a pharmaceutical composition for preventing or treating a heart failure and a method for screening a therapeutic agent for preventing or treating a heart failure. The pharmaceutical composition of the present disclosure comprises the CCN5 or CCN2”CT protein, or a genetic carrier comprising a nucleotide sequence encoding the CCN5 or the CCN2”CT protein, exhibiting dramatic prevention or treatment efficacies on a heart failure even without surgical treatments accompanied with transplanting a donor heart.
Abstract:
PURPOSE: A method for screening a therapeutic agent for heart failure, fibrosis, or inflammation is provided to suppress harmful heart remodeling and to activate PI3K/Akt/mTOR signal transduction pathway. CONSTITUTION: A method for screening a therapeutic agent for heart failure, fibrosis, or inflammation comprises: a step of treating a test material to cells containing Eya2(eyes absent 2) gene. The cells are derived from the heart. In case that the test material increases Eya2 gene expression, the test material is determined as a therapeutic agent for heart failure, fibrosis, or inflammation.
Abstract:
PURPOSE: A composition containing Eya2 gene is provided to effectively prevent or treat heart failure, fibrosis or inflammation. CONSTITUTION: A method for screening a therapeutic agent for preventing or treating heart failure, fibrosis or inflammation comprises: a step of treating test material to cells having Eya2 gene; and a step of analyzing the expression of Eya2 gene. In case of increase of Eya2 gene expression, the test material is considered as a therapeutic agent for preventing or treating heart failure, fibrosis or inflammation. A composition for preventing or treating heart failure, fibrosis or inflammation contains Eya2 gene as an active ingredient.
Abstract:
PURPOSE: A composition for preventing or treating heart failure is provided to change calcium sensitivity in cardiomyocytes using PKCζ(protein kinase C ζ) inhibitor. CONSTITUTION: A composition for preventing or treating heart failure contains PKCζ(protein kinase C ζ) inhibitor as an active ingredient. The PKCζ inhibitor is a compound of chemical formula I. In chemical formula I, R1 and R2 are independently alkoxycarbonyl group, substituted alkoxycarbonyl group, aryl group or substituted aryl group. At least one of R1 and R2 is alkoxycarbonyl group or substituted alkoxy carbonyl grouip.
Abstract:
본 발명은 7-아미노-4-((S)-3-(4-플루오로페닐)-2-((R)-3-메틸-2-(5-메틸이소옥사졸-3-카복사미도)부탄아미도)프로판아미도)-7-옥소-2-헵테노에이트 유도체, 이의 제조방법 및 이를 유효성분으로 함유하는 바이러스성 질환의 예방 및 치료용 약학적 조성물에 관한 것으로, 특히, 본 발명의 하기 화학식 1로 표시되는 유도체는 숙주세포 내로 침투한 바이러스의 복제 사이클에서 가장 중요한 역할을 하는 3C 프로테아제의 활성을 억제함으로써, 콕사키바이러스뿐만 아니라, 리노바이러스 등의 감염으로 인해 발생하는 일반 감기를 포함한 바이러스성 질환의 예방 및 치료제로 유용하게 이용될 수 있다. [화학식 1]
(상기 식에서, R은 명세서에 정의된 바와 같다.) 콕사키바이러스, 리노바이러스, 3C 프로테아제, 저해제
Abstract:
The present invention relates to a method for determining substrate specificity of a protease by employing a microorganism cotransformed with a vector expressing the protease and a vector expressing the substrate. The method comprises constructing an expression vector containing a gene for protease; constructing an expression vector containing genes for Golgi recognition signal and transmembrane domain of membrane protein locating at yeast Golgi complex, substrate domain with specific amino acid sequence, and yeast invertase; preparing a transformant by cotransforming suc2 mutant yeast with the two expression vectors; and, determining viability of the transformant in a medium containing a sole carbon source of sucrose. The invented method requires neither isolation/purification of protease nor synthesis of expensive substrate peptide. The simple and cost-effective determination of substrate specificity of proteases can be realized to allow its wide application in the identification of genes for proteases or genes for proteins cleaved with the proteases.