ALA-A2 Is a Novel Anticancer Peptide Inspired by Alpha-Lactalbumin: A Discovery from a Computational Peptide Library, In Silico Anticancer Peptide Screening and In Vitro Experimental Validation
Issued Date
2023-03-01
Resource Type
eISSN
20566646
Scopus ID
2-s2.0-85146263571
Journal Title
Global Challenges
Volume
7
Issue
3
Rights Holder(s)
SCOPUS
Bibliographic Citation
Global Challenges Vol.7 No.3 (2023)
Suggested Citation
Lerksuthirat T., On-yam P., Chitphuk S., Stitchantrakul W., Newburg D.S., Morrow A.L., Hongeng S., Chiangjong W., Chutipongtanate S. ALA-A2 Is a Novel Anticancer Peptide Inspired by Alpha-Lactalbumin: A Discovery from a Computational Peptide Library, In Silico Anticancer Peptide Screening and In Vitro Experimental Validation. Global Challenges Vol.7 No.3 (2023). doi:10.1002/gch2.202200213 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/82804
Title
ALA-A2 Is a Novel Anticancer Peptide Inspired by Alpha-Lactalbumin: A Discovery from a Computational Peptide Library, In Silico Anticancer Peptide Screening and In Vitro Experimental Validation
Other Contributor(s)
Abstract
Anticancer peptides (ACPs) are rising as a new strategy for cancer therapy. However, traditional laboratory screening to find and identify novel ACPs from hundreds to thousands of peptides is costly and time consuming. Here, a sequential procedure is applied to identify candidate ACPs from a computer-generated peptide library inspired by alpha-lactalbumin, a milk protein with known anticancer properties. A total of 2688 distinct peptides, 5–25 amino acids in length, are generated from alpha-lactalbumin. In silico ACP screening using the physicochemical and structural filters and three machine learning models lead to the top candidate peptides ALA-A1 and ALA-A2. In vitro screening against five human cancer cell lines supports ALA-A2 as the positive hit. ALA-A2 selectively kills A549 lung cancer cells in a dose-dependent manner, with no hemolytic side effects, and acts as a cell penetrating peptide without membranolytic effects. Sequential window acquisition of all theorical fragment ions-proteomics and functional validation reveal that ALA-A2 induces autophagy to mediate lung cancer cell death. This approach to identify ALA-A2 is time and cost-effective. Further investigations are warranted to elucidate the exact intracellular targets of ALA-A2. Moreover, these findings support the use of larger computational peptide libraries built upon multiple proteins to further advance ACP research and development.