Integrated computational and experimental identification of a novel ML-IAP-targeting peptide with antiproliferative activity in leukaemia cells.

Authors

Yan Wan, Yaozhi Hu, Ye Hong, Yanming Zhang, Na Hu, Jinrong Yao, Wenhui Fu, Xiaotian Yang, Junshuai Yue

Published in

Journal of enzyme inhibition and medicinal chemistry. Volume 41. Issue 1. Pages 2724128. Epub Sep 28, 2026.

Abstract

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 K_d value and a lower K_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.

PMID:
42805778
Bibliographic data and abstract were imported from PubMed on 29 Sep 2026.

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