Kundu Nikita, Sharma Taniya, Kaur Sarvpreet, Mahto Aman Kumar, Prasad Dewangan Rikeshwer, Shankaraswamy J, Saxena Sarika
Amity Institute of Biotechnology, Amity University Uttar Pradesh, Noida, India.
Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India.
J Biomol Struct Dyn. 2023 Sep-Oct;41(15):7119-7127. doi: 10.1080/07391102.2022.2116602. Epub 2022 Aug 29.
Human telomere is composed of highly repeated hexanucleotide sequence TTAGGG and a 3' single-stranded DNA tail. Many telomere G4 topologies characterized at atomic level by X-ray crystallography and NMR studies. Until now, various small ligands developed to interact with G-quadruplex mainly to stabilize the structure and least is known for its destabilization. In this study, we provide the first evidence of human telomeric G4 destabilization upon peptide binding in dilute and cell-mimicking molecular crowing conditions due to the changes in flanking bases of human telomeric sequences. Hence, our findings will open the new ways to target diseases related with increasing the efficiency of DNA replication, transcription or duplex reannealing.Communicated by Ramaswamy H. Sarma.
人类端粒由高度重复的六核苷酸序列TTAGGG和一个3'单链DNA尾巴组成。许多端粒G4拓扑结构已通过X射线晶体学和核磁共振研究在原子水平上得到表征。到目前为止，开发的各种与G-四链体相互作用的小配体主要是为了稳定结构，而关于其去稳定作用的了解最少。在本研究中，我们首次证明，在稀释和模拟细胞的分子拥挤条件下，由于人类端粒序列侧翼碱基的变化，肽结合会导致人类端粒G4去稳定。因此，我们的发现将为靶向与提高DNA复制、转录或双链重退火效率相关的疾病开辟新途径。由拉马斯瓦米·H·萨尔马传达。
