C-terminal modification of a de novo designed antimicrobial peptide via capping of macrolactam rings
Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review
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Detail(s)
Original language | English |
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Article number | 106251 |
Journal / Publication | Bioorganic Chemistry |
Volume | 130 |
Online published | 5 Nov 2022 |
Publication status | Published - Jan 2023 |
Link(s)
Abstract
In this work, by capping a macrolactam ring at the C-terminus of a de novo-designed peptide, namely zp80, we have constructed a small peptide library via the solid phase peptide synthesis for screening. Eight peptides bearing different aspartic acid-rich macrolactam rings but the same linear (IIRR)4 unit exhibited improved antibacterial activities, hemolytic activity, and selectivity index. Mechanistic studies revealed that they could destroy the integrity of bacterial envelope, leading to cytoplasm leakage and rapid dissipation of membrane potential. One of these peptides, zp90 with a macrolactam ring of (KaDGD), demonstrated preferential interaction with calcium ions at a stoichiometric ratio of 1:1, promoting the affinity of designed peptides to bacterial membrane. Overall, this work provides a feasible strategy for medicinal chemists to further develop potent, selective, and multifunctional de novo-designed antimicrobial peptides.
Research Area(s)
- Antimicrobial peptide, Calcium ion-binding affinity, Macrolactam ring, Membrane potential, Selectivity index
Citation Format(s)
C-terminal modification of a de novo designed antimicrobial peptide via capping of macrolactam rings. / Zeng, Ping; Cheng, Qipeng; Yi, Lanhua et al.
In: Bioorganic Chemistry, Vol. 130, 106251, 01.2023.
In: Bioorganic Chemistry, Vol. 130, 106251, 01.2023.
Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review