Effect of a C-end rule Modification on Antitumor Activity of Thymosin α1.

Effect of a C-end rule Modification on Antitumor Activity of Thymosin α1. Biochimie. 2018 Aug 07;: Authors: Wang F, Xu C, Peng R, Li B, Shen X, Zheng H, Lao X Abstract Thymosin α1 (Tα1), a hormone containing 28 amino acids, has been approved in several cancer therapies, but the lack of tumor-targeting hinders its full use in tumor treatment. We designed a new peptide by connecting Tα1 and RGDR, generating a product, Tα1-RGDR, where RGDR is located in the C-end with both tumor-homing and cell internalizing properties (C-end rule peptides, a consensus R/KXXR/K motif). This work aimed to study the antitumor and immunological activities of Tα1-RGDR, and its differences compared with the wild-type Tα1. The antitumor and immunological activities of Tα1-RGDR were measured using the B16F10 tumor and immunologic suppression models. The folding of Tα1-RGDR was monitored using circular dichroism (CD) spectroscopy. Tα1-RGDR treatment led to significant inhibition of tumor growth at a dose at which Tα1 showed a slight effect in the B16F10 tumor growth model. In the immunologic suppression model, Tα1-RGDR shared almost equivalent immunomodulatory effect with Tα1. These results demonstrated the better therapeutic effects after treatment with Tα1-RGDR compared with Tα1. Moreover, both Tα1-RGDR and Tα1 shared a helical conformation in the presence of trifluoroethanol based on CD spectroscopy. Our dock information of Tα1-RGDR when ...
Source: Biochimie - Category: Biochemistry Authors: Tags: Biochimie Source Type: research