Anselmi Michele, Baiula Monica, Santino Federica, Zhao Junwei, Spampinato Santi, Calonghi Natalia, Gentilucci Luca
Department of Chemistry "G. Ciamician", University of Bologna, Via Selmi 2, 40126 Bologna, Italy.
Department of Pharmacy and Biotechnology, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy.
Biomedicines. 2021 Nov 21;9(11):1737. doi: 10.3390/biomedicines9111737.
Arg-Gly-Asp (RGD)-binding integrins, e.g., αvβ3, αvβ1, αvβ5 integrins, are currently regarded as privileged targets for the delivery of diagnostic and theranostic agents, especially in cancer treatment. In contrast, scarce attention has been paid so far to the diagnostic opportunities promised by integrins that recognize other peptide motifs. In particular, α4β1 integrin is involved in inflammatory, allergic, and autoimmune diseases, therefore, it represents an interesting therapeutic target. Aiming at obtaining simple, highly stable ligands of α4β1 integrin, we designed hybrid α/β peptidomimetics carrying linkable side chains for the expedient functionalization of biomaterials, nano- and microparticles. We identified the prototypic ligands MPUPA-()-isoAsp(NHPr)-Gly-OH () and MPUPA-Dap(Ac)-Gly-OH () (MPUPA, methylphenylureaphenylacetic acid; Dap, 2,3-diamino propionic acid). Modification of and by introduction of flexible linkers at isoAsp or Dap gave and , respectively, which allowed for coating with monolayers (ML) of flat zeolite crystals. The resulting peptide-zeolite MLs were able to capture selectively α4β1 integrin-expressing cells. In perspective, the α4β1 integrin ligands identified in this study can find applications for preparing biofunctionalized surfaces and diagnostic devices to control the progression of α4β1 integrin-correlated diseases.
精氨酸-甘氨酸-天冬氨酸（RGD）结合整合素，例如αvβ3、αvβ1、αvβ5整合素，目前被视为诊断和治疗诊断剂递送的优先靶点，尤其是在癌症治疗中。相比之下，迄今为止，对于识别其他肽基序的整合素所带来的诊断机会关注较少。特别是，α4β1整合素参与炎症、过敏和自身免疫性疾病，因此，它是一个有趣的治疗靶点。为了获得简单、高度稳定的α4β1整合素配体，我们设计了带有可连接侧链的α/β肽模拟物，以便对生物材料、纳米颗粒和微粒进行便捷的功能化修饰。我们鉴定出了原型配体MPUPA-()-异天冬氨酸(NHPr)-甘氨酸-OH ()和MPUPA-二氨基丙酸(Ac)-甘氨酸-OH ()（MPUPA，甲基苯基脲苯基乙酸；Dap，2,3-二氨基丙酸）。通过在异天冬氨酸或二氨基丙酸处引入柔性接头对 和 进行修饰，分别得到了 和 ，它们能够用扁平沸石晶体的单层（ML）进行包被。所得的肽-沸石ML能够选择性地捕获表达α4β1整合素的细胞。从长远来看，本研究中鉴定出的α4β1整合素配体可用于制备生物功能化表面和诊断设备，以控制与α4β1整合素相关疾病的进展。
