Laboratory of Oncology, Institute of Microbial Chemistry (BIKAKEN), Shinagawa-ku, Tokyo 141-0021, Japan.
Department of Environmental Biochemistry, Kyoto Pharmaceutical University, Yamashina, Kyoto 607-8414, Japan; Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
Bioorg Med Chem. 2022 Oct 1;71:116953. doi: 10.1016/j.bmc.2022.116953. Epub 2022 Aug 9.
Peptides have become an attractive drug discovery modality alongside small molecule compounds and high molecular weight biomolecules because they bind strongly to their target molecules. Previously, we found that secreted extracellular human GAPDH exhibits inhibitory activity against cancer cell growth. We sought to identify the minimal peptide sequence required for GAPDH activity in an effort to develop a small GAPDH-derived peptide with anti-cancer activity. Moreover, derivatives of the identified peptide, in which some amino acid residues were substituted with unnatural amino acids, were found to show stronger anti-cancer activity than non-substituted peptides.
肽已成为一种有吸引力的药物发现模式，与小分子化合物和高分子量生物分子一起，因为它们与靶分子结合紧密。此前，我们发现分泌的细胞外人类 GAPDH 对癌细胞生长具有抑制活性。我们试图确定 GAPDH 活性所需的最小肽序列，以开发具有抗癌活性的小 GAPDH 衍生肽。此外，所鉴定的肽的衍生物，其中一些氨基酸残基被非天然氨基酸取代，被发现比未取代的肽具有更强的抗癌活性。
