Paturel Vivien, Baud Stéphanie, Schneider Christophe, Brassart-Pasco Sylvie
Université de Reims Champagne-Ardenne, CNRS, MEDYC, F-51100 Reims, France.
Université de Reims Champagne-Ardenne, URCATech, P3M, F-51100 Reims, France.
Pharmaceuticals (Basel). 2025 Jun 21;18(7):940. doi: 10.3390/ph18070940.
: Tetrastatin, the globular non collagenous (NC1) domain of the α4 chain of collagen IV, was previously demonstrated to inhibit melanoma progression. We identified the minimal active sequence (QKISRCQVCVKYS: QS-13) that reproduced the anti-tumor effects of whole Tetrastatin and demonstrated its anti-angiogenic activity mediated through αvβ3 and α5β1 binding. As QS-13 peptide was not fully soluble in aqueous solution, we designed new peptides with better water solubility. The present work aimed to investigate the interactions of ten QS-13-derived peptides, exhibiting improved hydro-solubility, with αvβ3 and α5β1 integrins. : Using bioinformatics tools such as GROMACS, VMD, and the Autodock4 suite, we investigated the ability of the substituted peptides to bind αvβ3 and α5β1 integrins in silico. : We demonstrated in silico that all substituted peptides were able to bind both integrins at the RGD-binding site and determined their theoretical binding energy. : The new soluble peptides should be able to compete with natural integrin ligands such as fibronectin, but also FGF1, FGF2, IGF1, and IGF2. Taken together, these findings suggest that the QS-13-derived peptides are reliable anti-angiogenic and anti-tumor agents.
四聚他汀是IV型胶原α4链的球状非胶原（NC1）结构域，先前已证明其可抑制黑色素瘤进展。我们鉴定出了能重现完整四聚他汀抗肿瘤作用的最小活性序列（QKISRCQVCVKYS：QS - 13），并证明了其通过与αvβ3和α5β1结合介导的抗血管生成活性。由于QS - 13肽在水溶液中不完全溶解，我们设计了水溶性更好的新肽。本研究旨在探究十种具有改善水溶性的QS - 13衍生肽与αvβ3和α5β1整合素的相互作用。：使用诸如GROMACS、VMD和Autodock4套件等生物信息学工具，我们在计算机模拟中研究了取代肽与αvβ3和α5β1整合素结合的能力。：我们在计算机模拟中证明，所有取代肽都能够在RGD结合位点与两种整合素结合，并确定了它们的理论结合能。：新的可溶性肽应该能够与天然整合素配体如纤连蛋白竞争，也能与FGF1、FGF2、IGF1和IGF2竞争。综上所述，这些发现表明QS - 13衍生肽是可靠的抗血管生成和抗肿瘤药物。
