Rational Design and Delivery of Engineered Peptides: Toward a Unified Framework for Structure, Screening, and Application.
- 1School of Biological Science and Medical Engineering, Hunan University of Technology, Zhuzhou 412007, China.
- 2Yuelushan Laboratory, Hunan Academy of Agricultural Sciences, Changsha 410125, China.
- 3Hunan Key Laboratory of Economic Crops Genetic Improvement and Integrated Utilization, School of Life and Health Sciences, Hunan University of Science and Technology, Xiangtan 411201, China.
Abstract
This review presents a three-tiered engineering framework that systematically addresses these barriers. First, we survey chemical and sequence-based stabilization strategies, including lipidation, backbone N-methylation, and cyclization, that convert labile natural peptides into protease-resistant scaffolds. Second, moving beyond generic stabilization, we dissect the rational design of effector-inhibitory peptides, with particular emphasis on disulfide bond topology engineering as a powerful means to lock binding-competent conformations, alongside structure-guided interface optimization. Third, recognizing that purely rational design often fails to correctly fold complex topologies, we discuss complementary structure-constrained screening platforms (phage display, yeast display, and in silico docking) that exploit sequence-conformation coupling to enrich functional structures from vast libraries. Critically, we argue that these molecular-level designs can only achieve in vivo efficacy when co-integrated with delivery systems, including lipidic, polymeric, and viral carriers, which together determine bioavailability, targeting, and controlled release. By weaving these layers into a unified framework, we highlight a paradigm shift from sequential optimization toward context-aware co-design, where peptide rigidity, flexibility, affinity, and carrier compatibility are balanced against specific therapeutic or industrial contexts.
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BibTeX
@article{xie2026rational,
title = {{Rational Design and Delivery of Engineered Peptides: Toward a Unified Framework for Structure, Screening, and Application.}},
author = {Qijun Xie and Haiying Ma and Biao Liu and Li Yu and Yang Fang and Lili Liu and Mingli Yan},
journal = {Biology},
year = {2026},
month = oct,
doi = {10.3390/biology15191754},
url = {https://europepmc.org/article/MED/42883427},
note = {CC BY},
}
RIS
TY - JOUR
TI - Rational Design and Delivery of Engineered Peptides: Toward a Unified Framework for Structure, Screening, and Application.
AU - Qijun Xie
AU - Haiying Ma
AU - Biao Liu
AU - Li Yu
AU - Yang Fang
AU - Lili Liu
AU - Mingli Yan
PY - 2026
DA - 2026/10/02
JO - Biology
DO - 10.3390/biology15191754
UR - https://europepmc.org/article/MED/42883427
AB - This review presents a three-tiered engineering framework that systematically addresses these barriers. First, we survey chemical and sequence-based stabilization strategies, including lipidation, backbone N-methylation, and cyclization, that convert labile natural peptides into protease-resistant scaffolds. Second, moving beyond generic stabilization, we dissect the rational design of effector-inhibitory peptides, with particular emphasis on disulfide bond topology engineering as a powerful means to lock binding-competent conformations, alongside structure-guided interface optimization. Third, recognizing that purely rational design often fails to correctly fold complex topologies, we discuss complementary structure-constrained screening platforms (phage display, yeast display, and in silico docking) that exploit sequence-conformation coupling to enrich functional structures from vast libraries. Critically, we argue that these molecular-level designs can only achieve in vivo efficacy when co-integrated with delivery systems, including lipidic, polymeric, and viral carriers, which together determine bioavailability, targeting, and controlled release. By weaving these layers into a unified framework, we highlight a paradigm shift from sequential optimization toward context-aware co-design, where peptide rigidity, flexibility, affinity, and carrier compatibility are balanced against specific therapeutic or industrial contexts.
SN - 2079-7737
ER -