Dataset Information

High Cell Selectivity and Bactericidal Mechanism of Symmetric Peptides Centered on d-Pro-Gly Pairs.

ABSTRACT: Antimicrobial peptides (AMPs) have a unique action mechanism that can help to solve global problems in antibiotic resistance. However, their low therapeutic index and poor stability seriously hamper their development as therapeutic agents. In order to overcome these problems, we designed peptides based on the sequence template XXRXXRRzzRRXXRXX-NH₂, where X represents a hydrophobic amino acid like Phe (F), Ile (I), and Leu (L), while zz represents Gly-Gly (GG) or d-Pro-Gly (pG). Showing effective antimicrobial activity against Gram-negative bacteria and low toxicity, designed peptides had a tendency to form an ?-helical structure in membrane-mimetic environments. Among them, peptide LR_pG (X: L, zz: pG) showed the highest geometric mean average treatment index (GM_TI = 73.1), better salt, temperature and pH stability, and an additive effect with conventional antibiotics. Peptide LR_pG played the role of anti-Gram-negative bacteria through destroying the cell membrane. In addition, peptide LR_pG also exhibited an anti-inflammatory activity by effectively neutralizing endotoxin. Briefly, peptide LR_pG has the potential to serve as a therapeutic agent to reduce antibiotic resistance owing to its high therapeutic index and great stability.

SUBMITTER: Jia BY

PROVIDER: S-EPMC7037546 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

High Cell Selectivity and Bactericidal Mechanism of Symmetric Peptides Centered on d-Pro-Gly Pairs.

Jia Bo-Yan BY Wang Yi-Ming YM Zhang Ying Y Wang Zi Z Wang Xue X Muhammad Inam I Kong Ling-Cong LC Pei Zhi-Hua ZH Ma Hong-Xia HX Jiang Xiu-Yun XY

International journal of molecular sciences 20200208 3

Antimicrobial peptides (AMPs) have a unique action mechanism that can help to solve global problems in antibiotic resistance. However, their low therapeutic index and poor stability seriously hamper their development as therapeutic agents. In order to overcome these problems, we designed peptides based on the sequence template XXRXXRRzzRRXXRXX-NH<sub>2</sub>, where X represents a hydrophobic amino acid like Phe (F), Ile (I), and Leu (L), while zz represents Gly-Gly (GG) or d-Pro-Gly (pG). Showin ...[more]

PMID: 32046328

Similar Datasets

Project description:N(G)-Methylation of arginine residues in many nucleic-acid-binding proteins are formed post-translationally, catalysed by S-adenosylmethionine:protein-arginine N-methyltransferase in their glycine-rich and arginine-rich motifs. The amino acid sequences of the stimulator of HIV-1 TAR (Tat-responsive element) RNA-binding protein (SRB) and fibronectin also show the presence of the internal -Gly-Arg-Gly- (-GRG-) sequence, which is potentially methylatable by the methyltransferase. To investigate the sequence requirement for methylation of these proteins, several synthetic oligopeptides with different chain lengths and sequences similar to the -GRG- regions of SRB and fibronectin were synthesized. Whereas the heptapeptide AGGRGKG (residues 16-22 in SRB) served as the methyl acceptor for the methyltransferase with a K(m) of 50 microM, the 19-mer peptide (residues 10-28 in SRB) was methylated with a K(m) of 8.3 microM, indicating that a greater peptide chain length yields a better methyl acceptor. Product analysis of the methylated [methyl-(14)C]SRB-peptide by HPLC indicated the formation of N(G)-monomethylarginine and N(G),N(G)-dimethyl(asymmetric)arginine. Synthetic peptides containing the cell attachment sequence [Arg-Gly-Asp ('RGD')] in fibronectin, GRGDSPK, GGRGDSPK and GGGRGDSPK, were also studied; whereas GRGDSPK was a poor methyl acceptor, the longer peptides were better methyl acceptors. To provide an understanding of the effect of methylation on fibronectin peptide, arginine-unmethylated and methylated GGRGDSPK were compared for their effect on the mitogenesis induced by beta-hexosaminidase A and an agonistic antibody (mAb(15)) in bovine tracheal smooth-muscle cells; whereas the former inhibited 35-67% of mitogenesis at a concentration of 5-10 microM, the latter did not block mitogenesis. This lack of inhibition by the insertion of a methyl group on the arginyl residue of the cell attachment sequence might be due to the hindrance of the binding of fibronectin peptide to integrins.

Dataset Information

High Cell Selectivity and Bactericidal Mechanism of Symmetric Peptides Centered on d-Pro-Gly Pairs.

Publications

High Cell Selectivity and Bactericidal Mechanism of Symmetric Peptides Centered on d-Pro-Gly Pairs.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets