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烷氧羰基修饰的六肽作为治疗银屑病中对Wnt5A蛋白具有高亲和力的化合物。

Alkyloxy carbonyl modified hexapeptides as a high affinity compounds for Wnt5A protein in the treatment of psoriasis.

作者信息

Kelotra Ankit, Gokhale Sadashiv M, Kelotra Seema, Mukadam Vaidehi, Nagwanshi Komal, Bandaru Srinivas, Nayarisseri Anuraj, Bidwai Anil

机构信息

School of Biochemistry, Devi Ahilya University, Takshashila Campus, Khandwa Road, Indore (M.P.) - 452 017, India.

M.B Khalsa College, Near Gangwal Bus Stand, Indore (M.P.)-452011, India.

出版信息

Bioinformation. 2014 Dec 31;10(12):743-9. doi: 10.6026/97320630010743. eCollection 2014.

Abstract

Psoriasis is one of the most prevalent chronic inflammatory diseases of the skin. The Wnt pathways have been documented to play essential role in stem cell self-renewal and keratinocyte differentiation in the skin. Antagonizing the Wnt5a protein would emerge as a novel therapeutics in psoriasis treatment. In this view, we have developed and characterized series of compounds by attaching varied tertiary alkyloxy carbonyl groups at the N-terminal end of the hexapeptide (Met-Asp-Gly-Cys-Glu-Leu) bestowed to inhibit Wnt/Ca2+ signaling in psoriasis. Hexapeptide compound with 1,1-diphenylethoxy carbonyl group attached to N-terminal end of hexapeptide demonstrated highest binding affinity amongst all the evaluated compounds. The compound identified in the study can be subjected further for in vitro and in vivo studies for ADMET properties.

摘要

银屑病是最常见的慢性皮肤炎症性疾病之一。已有文献证明,Wnt信号通路在皮肤干细胞自我更新和角质形成细胞分化中起关键作用。拮抗Wnt5a蛋白将成为银屑病治疗的一种新型疗法。基于此观点,我们通过在六肽(Met-Asp-Gly-Cys-Glu-Leu)的N端连接不同的叔烷基氧羰基基团,开发并表征了一系列化合物,该六肽被赋予抑制银屑病中Wnt/Ca2+信号传导的功能。在六肽N端连接1,1-二苯乙氧基羰基基团的六肽化合物在所有评估化合物中表现出最高的结合亲和力。该研究中鉴定出的化合物可进一步进行体外和体内的ADMET性质研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/536c/4312367/da60bf09b374/97320630010743F1.jpg

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