Screened peptides from one-bead one-compound technique extend half-life of peptide drugs in circulation through binding to albumin

• Published in: Chinese chemical letters 2024-03, Vol.35 (3), p.108530, Article 108530
• Main Authors: Li, Yi-Jing, Zhang, Lingze, Pang, Ming-Hao, Yang, Pei-Pei, Guo, Lu-Ming, Zhang, Kuo, Hou, Da-Yong, Wang, Lei, Wang, Hao, Cao, Hui
• Format: Article
• Language: English
• Subjects: Albumin binding; Combinatorial library; Drug delivery; One-bead one-compound; Triptorelin
• ISSN: 1001-8417; 1878-5964
• DOI: 10.1016/j.cclet.2023.108530

Peptide drugs are known for their high biological safety. However, compared with small molecule drugs, peptide drugs are easily oxidized and hydrolyzed as well as short in half-life. Herein, inspired by the long circulation of albumin in blood, we screened albumin binding peptides (ABPs) from a one-bead one-compound (OBOC) peptide library to increase the half-life of peptide drugs. Beads displaying random peptides were screened using fluorescent labeled human serum albumin. Fluorescent beads with specific binding to albumin were isolated for sequencing. The selected ABPs can effectively bind to albumin, thus possessing the long circulation of albumin. The dissociation constant (KD) of ABPs to albumin is up to 1 × 10−8 mol/L. Once one of ABPs (ABP2) was coupled to triptorelin, the circulation half-life of triptorelin in mice was significantly prolonged to 263.50 h much longer than that of triptorelin alone (179.07 h). In addition, the combination therapy using ABP-conjugated triptorelin and doxorubicin (DOX) can effectively inhibit the proliferation of tumor cells in mice. The OBOC screening strategy and resulting ABPs showed great potential for enhancing the delivery efficiency of peptide drugs. Schematic diagram of one-bead one-compound (OBOC) screening strategy for albumin-binding peptides (ABPs), inspired by the long-circulating properties of human serum albumin. ABPs can effectively prolong the half-life of triptorelin and enhance the efficacy of doxorubicin (DOX) against triple-negative breast cancer in a mouse model. [Display omitted]