Solvent-Free procedure of an A9 Peptide Dimer Exhibiting Specific HER2 Receptor Binding: Fluorescence Spectroscopy Evaluation of the Enhanced Binding Affinity

HER2-expressing cancers currently benefit from targeted
therapies,
including monoclonal antibodies and antibody-drug conjugates that
specifically bind to the extracellular domain of the receptor. Peptides
targeting HER2 represent promising candidates for the development
of alternative molecular drugs. In this study, we report a dimeric
version of the previously validated A9 peptide as a ligand specifically
targeting HER2. The novel A9-PEG-A9 conjugate consists of two A9 peptides
whose N-terminal amino groups are linked via a polyethylene glycol
chain. It was synthesized using a solvent-free protocol and validated
as an improved ligand, demonstrating enhanced water solubility and
increased affinity for the model receptor HER2-DIVMP, as determined
by the fluorescence spectroscopy titration method.

人表皮生长因子受体2（HER2）阳性癌症目前可从靶向治疗中获益，此类治疗手段包括特异性结合该受体胞外结构域的单克隆抗体与抗体偶联药物。靶向HER2的肽类是开发替代性分子药物的极具潜力的候选药物。本研究报道了一款经前期验证的A9肽的二聚体形式，作为特异性靶向HER2的配体。该新型A9-PEG-A9结合物包含两段A9肽，二者的N端氨基通过聚乙二醇（Polyethylene Glycol）链相连。该结合物采用无溶剂合成方案制备，并被验证为一款优化后的配体：经荧光光谱滴定法测定，其对模型受体HER2-DIVMP的水溶性显著提升，结合亲和力亦有所增强。