2026-10-11T13:18:16Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34018879 2026-09-29T01:40:02Z category_1 category_4 category_12 category_14 category_16 category_19 category_21 category_873 category_46 category_734 category_64 category_128 portal_87 item_type_6 month_year_09_2026

Integrated computational and experimental identification of a novel ML-IAP-targeting peptide with antiproliferative activity in leukaemia cells Yan Wan (342234) Yaozhi Hu (23615754) Ye Hong (2580841) Yanming Zhang (432346) Na Hu (115586) Jinrong Yao (1430950) Wenhui Fu (9152589) Xiaotian Yang (4101355) Junshuai Yue (25133656) Biophysics Biochemistry Cell Biology Molecular Biology Physiology Pharmacology Biotechnology Chemical Sciences not elsewhere classified Immunology Biological Sciences not elsewhere classified Cancer Hematology Leukaemia ML-IAP peptide virtual screening experimental validation <p>Melanoma inhibitor of apoptosis protein (ML-IAP) is an IAP family member involved in tumour cell survival and a potential target in ML-IAP-expressing leukaemia. Here, 59 319 tetrapeptides were screened against ML-IAP by molecular docking, and four top-ranked peptides were selected. Microscale thermophoresis confirmed binding of peptides 1–4 to ML-IAP, with peptide-1 showing the lowest <i>K</i>_d value and a lower <i>K</i>_d value than the Smac peptide. Structure–activity relationship (SAR) analysis indicated that peptide-1 had more favourable ML-IAP recognition features. A molecular dynamics simulation, molecular mechanics/Poisson–Boltzmann surface area (MM/PBSA) calculations and free-energy landscape analysis supported the relative conformational stability of the ML-IAP–peptide-1 complex. MTT assays showed that peptide-1 inhibited MOLT-4, MOLM-13, and MV-4-11 cell proliferation, with limited inhibitory activity against HS-27A cells. ML-IAP knockdown reduced peptide-1 activity, while peptide-1 increased the cleaved/total caspase-3 ratio and altered Bax and Bcl-2 mRNA expression. These results suggest that peptide-1 may represent an ML-IAP-targeting peptide with antiproliferative activity in leukaemia cells.</p> 2026-09-29T01:40:02Z Text Journal contribution 10.6084/m9.figshare.34018879.v1 https://figshare.com/articles/journal_contribution/Integrated_computational_and_experimental_identification_of_a_novel_ML-IAP-targeting_peptide_with_antiproliferative_activity_in_leukaemia_cells/34018879 CC BY 4.0