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These so-called non-canonical peptides offer significant potential for modifying biological, pharmacological, and physiochemical characteristics in both native and synthetic contexts. Despite their advantages, there remains a notable gap in the availability of an efficient pre-trained model capable of effectively capturing feature representations from such intricate peptide sequences. This study herein introduces PepLand, a novel pre-training framework designed for the comprehensive representation and analysis of peptides, encompassing both canonical and non-canonical amino acids. PepLand leverages a general-purpose multi-view heterogeneous graph neural network to unveil the subtle structural representations of peptides. Our empirical evaluations demonstrate PepLand\u2019s proficiency in a range of peptide property prediction tasks, including cell penetrability, solubility, and protein\u2013peptide binding affinity. These rigorous assessments affirm PepLand\u2019s superior capability in discerning critical representations of peptides with both canonical and non-canonical amino acids, and provide a robust foundation for transformative advances in peptide-focused pharmaceutical research. We have made the entire source code and datasets available at http:\/\/www.healthinformaticslab.org\/supp\/resources.php or https:\/\/github.com\/zhangruochi\/PepLand<\/jats:p>","DOI":"10.1093\/bib\/bbaf367","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T13:36:06Z","timestamp":1754055366000},"source":"Crossref","is-referenced-by-count":9,"title":["PepLand: a large-scale pre-trained peptide representation model for a comprehensive landscape of both canonical and non-canonical amino acids"],"prefix":"10.1093","volume":"26","author":[{"given":"Ruochi","family":"Zhang","sequence":"first","affiliation":[{"name":"Key Laboratory of Symbolic Computation and Knowledge Engineering of Ministry of Education, Jilin University, Changchun , Jilin 130012 ,","place":["China"]},{"name":"School of Artificial Intelligence, Jilin University , Changchun 130012 ,","place":["China"]},{"name":"Syneron Technology , Guangzhou 510700 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoran","family":"Wu","sequence":"additional","affiliation":[{"name":"Syneron Technology , Guangzhou 510700 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Liu","sequence":"additional","affiliation":[{"name":"Beijing Life Science Academy , Beijing 102209 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Symbolic Computation and Knowledge Engineering of Ministry of Education, Jilin University, Changchun , Jilin 130012 ,","place":["China"]},{"name":"College of Computer Science and Technology Jilin University, Changchun , Jilin 130012 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Xiu","sequence":"additional","affiliation":[{"name":"Syneron Technology , Guangzhou 510700 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King Abdullah University of Science and Technology (KAUST) Thuwal , Thuwal 23955 ,","place":["Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8108-6007","authenticated-orcid":false,"given":"Fengfeng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Symbolic Computation and Knowledge Engineering of Ministry of Education, Jilin University, Changchun , Jilin 130012 ,","place":["China"]},{"name":"College of Computer Science and Technology Jilin University, Changchun , Jilin 130012 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,8,1]]},"reference":[{"key":"2025080109360229100_ref1","doi-asserted-by":"publisher","first-page":"6553","DOI":"10.1039\/C7CS00536A","article-title":"Molecular engineering solutions for therapeutic peptide delivery","volume":"46","author":"Acar","year":"2017","journal-title":"Chem Soc 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